Seven Novel Mammalian SNARE Proteins Localize to Distinct Membrane Compartments

Abstract

Soluble N-ethylmaleimide-sensitive factor-attachment protein receptor (SNARE) proteins of the vesicle-associated membrane protein (VAMP) and syntaxin families play a central role in vesicular trafficking through the formation of complexes between proteins present on vesicle and target membranes. Formation of these complexes is proposed to mediate aspects of the specificity of vesicle trafficking and to promote fusion of the lipid bilayers. In order to further understand the molecular mechanisms that organize membrane compartments, we have characterized seven new mammalian proteins of the VAMP and syntaxin families. The proteins are broadly expressed; however, syntaxin 13 is enriched in brain and VAMP 8 in kidney. The seven novel SNAREs localize in distinct patterns overlapping with Golgi, endosomal, or lysosomal markers. Our studies support the hypothesis that evolutionary radiation of these two gene families gave rise to sets of proteins whose differential expression and combinatorial associations define and organize the membrane compartments of cells. Soluble N-ethylmaleimide-sensitive factor-attachment protein receptor (SNARE) proteins of the vesicle-associated membrane protein (VAMP) and syntaxin families play a central role in vesicular trafficking through the formation of complexes between proteins present on vesicle and target membranes. Formation of these complexes is proposed to mediate aspects of the specificity of vesicle trafficking and to promote fusion of the lipid bilayers. In order to further understand the molecular mechanisms that organize membrane compartments, we have characterized seven new mammalian proteins of the VAMP and syntaxin families. The proteins are broadly expressed; however, syntaxin 13 is enriched in brain and VAMP 8 in kidney. The seven novel SNAREs localize in distinct patterns overlapping with Golgi, endosomal, or lysosomal markers. Our studies support the hypothesis that evolutionary radiation of these two gene families gave rise to sets of proteins whose differential expression and combinatorial associations define and organize the membrane compartments of cells. The distribution and restriction of molecules to membrane compartments is an essential process of eukaryotic cells. Distinct organelles of the secretory pathway are synthesized and maintained by budding of transport vesicles from a donor compartment followed by fusion of these vesicles with an acceptor membrane (1Palade G. Science. 1975; 189: 347-358Crossref PubMed Scopus (2322) Google Scholar). The molecular mechanisms responsible for vesicle biogenesis, protein sorting, and membrane fusion are not yet fully understood. While yeast genetics,in vitro biochemistry, and studies of synaptic vesicles have identified many of the components essential for these processes (2Rothman J.E. Nature. 1994; 372: 55-63Crossref PubMed Scopus (1995) Google Scholar, 3Bennett M.K. Scheller R.H. Annu. Rev. Biochem. 1994; 63: 63-100Crossref PubMed Scopus (233) Google Scholar, 4Jahn R. Südhof T.C. Annu. Rev. Neurosci. 1994; 17: 219-246Crossref PubMed Scopus (335) Google Scholar), the full repertoire of important proteins and their mechanisms of action are yet to be determined. One particularly interesting issue is how a vesicle loaded with specific cargo recognizes the appropriate target. It is becoming clear that several independent mechanisms contribute to the specificity of vesicle trafficking, and it is the sum of these multiple layers of specificity that results in a process with high fidelity (5Scheller R.H. Neuron. 1995; 14: 893-897Abstract Full Text PDF PubMed Scopus (196) Google Scholar).A vesicle-target membrane recognition event mediated by interaction of integral membrane proteins of the vesicle (v-SNAREs) 1The abbreviations used are: v-SNARE, SNARE on vesicle; ER, endoplasmic reticulum; EST, expressed sequence tag; lgp120, lysosomal glycoprotein of 120 kDa; NRK, normal rat kidney; PCR, polymerase chain reaction; SNAP-25, synaptosome-associated protein of 25 kDa, SNARE, soluble N-ethylmaleimide-sensitive factor-attachment protein receptor; TGN, trans-Golgi network; t-SNARE, SNARE on target membrane; VAMP, vesicle-associated membrane protein; bp, base pair(s); kb, kilobase(s). 1The abbreviations used are: v-SNARE, SNARE on vesicle; ER, endoplasmic reticulum; EST, expressed sequence tag; lgp120, lysosomal glycoprotein of 120 kDa; NRK, normal rat kidney; PCR, polymerase chain reaction; SNAP-25, synaptosome-associated protein of 25 kDa, SNARE, soluble N-ethylmaleimide-sensitive factor-attachment protein receptor; TGN, trans-Golgi network; t-SNARE, SNARE on target membrane; VAMP, vesicle-associated membrane protein; bp, base pair(s); kb, kilobase(s). and target (t-SNAREs) membranes represents one layer of targeting specificity, acting at the final step of membrane fusion (6Bennett M.K. Garcia-Arraras J.E. Elferink L.A. Peterson K. Fleming A.M. Hazuka C.D. Scheller R.H. Full Text PDF PubMed Scopus Google Scholar, J.E. Nature. PubMed Scopus Google Scholar). process in the mammalian formation of a between the v-SNARE, or and the syntaxin and is to a membrane recognition and fusion of the lipid T.C. Nature. 1995; PubMed Scopus Google Scholar, Scheller R.H. Neuron. Full Text Full Text PDF PubMed Scopus Google proteins have to be of gene families that membrane compartments (6Bennett M.K. Garcia-Arraras J.E. Elferink L.A. Peterson K. Fleming A.M. Hazuka C.D. Scheller R.H. Full Text PDF PubMed Scopus Google Scholar). syntaxin in yeast have to the G. 1994; PubMed Scopus Google Scholar), PubMed Scopus Google Scholar), Nature. PubMed Scopus Google Scholar), and the membrane and M.K. PubMed Scopus Google Scholar). In the SNAREs present on yeast have and support the that a and a are on membranes for target recognition and membrane fusion Nature. PubMed Scopus Google Scholar). these studies that of the syntaxin and VAMP families define membrane compartments and that specific of these proteins represents a of the specificity of vesicle studies to have to that not vesicle trafficking a distinct the sequence of the yeast the syntaxin and VAMP that be by sequence have the and multiple and of to yeast the of are present in the yeast a of the base of mammalian expressed sequence proposed the of at mammalian Scheller R.H. Nature. PubMed Scopus Google Scholar). In order to fully understand the of membrane compartments in mammalian it to further the of SNARE we have characterized seven new mammalian proteins that we to be SNAREs important in membrane While of the new SNAREs are are enriched in specific an for trafficking in cells. The proteins are to the and a role in membrane trafficking to and from these of identified from the from and of with the yeast sequence PubMed Scopus Google Scholar). distinct sets of The with the sequence The with an of however, it an to at a is from bp, base are from and are from an of of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we a brain and used to a sequence the brain a for the polymerase chain The by a and used to from a rat brain and overlapping The an syntaxin distribution and membrane of syntaxin 13 Scheller R.H. Full Text Full Text PDF PubMed Scopus Google of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we a of that it an for the protein syntaxin of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we a of that it a for the protein VAMP of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we an of that it a for the protein VAMP of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we used in a with a rat The the eukaryotic expression and and and 13 by with with appropriate restriction The the VAMP and and or mammalian expression the by syntaxin 13 a to of syntaxin and used for at The specificity of the by the of to the in not used at a receptor at a of at and at and multiple from with with used for syntaxin used for VAMP and VAMP and a rat used for VAMP for in for at and for at in at high in at a and maintained PubMed Scopus Google Scholar). rat the with and Scheller R.H. Full Text Full Text PDF PubMed Scopus Google sequence and protein the of G. Scholar). the PubMed Google that or and syntaxin with to a that membranes or in the fusion of membranes Scheller R.H. Neuron. Full Text Full Text PDF PubMed Scopus Google Scholar, R. R. J.E. Full Text Full Text PDF PubMed Scopus Google Scholar). complexes of syntaxin and VAMP have for to and to trafficking Scheller R.H. Full Text Full Text PDF PubMed Scopus Google Scholar, Scheller R.H. PubMed Scopus Google Scholar). The formation of complexes between of these families is specific sets of proteins Scheller R.H. Full Text Full Text PDF PubMed Scopus Google Scholar). it is clear that mechanisms play a role in the transport of vesicles to target specific SNARE is for appropriate membrane rise to the that the of SNARE proteins of the VAMP and syntaxin families define sets of membranes that have the to with on the of the proteins to SNARE protein is a event membrane fusion the of VAMP and syntaxin to the vesicle or target membranes In we define the of novel mammalian SNARE proteins through the of have used and a of SNARE proteins Scheller R.H. Full Text Full Text PDF PubMed Scopus Google Scholar). in the it for to base on that of the the of to we have used to the of the Golgi, syntaxin to the receptor to and to While of the by these is in the to one of the of the specific patterns a on the proteins characterized in are in the a of organelles are studies be to define the membrane compartments by of the in that are trafficking proteins and between donor and acceptor membranes. While studies the of the at the these SNAREs are interesting is VAMP that protein with the lysosomal protein the trafficking VAMP is with from to VAMP be an present at on transport vesicles to the with a high on the VAMP be a present at on vesicles to membrane It is that VAMP a vesicle receptor for are of the of and be Scheller R.H. PubMed Scopus Google Scholar).A of the between and is becoming on the sequence are at of the mammalian syntaxin gene two are to The the syntaxin syntaxin to the membrane and syntaxin to the and 13 to The syntaxin to the TGN, and Scheller R.H. PubMed Scopus Google Scholar). the mammalian are to be that not are the of one that in the and proteins have one gene that to mediate the of membrane in these to have fusion processes the of and is in fusion a of fusion through Nature. PubMed Scopus Google a the or a of proposed a evolutionary The of seven the and and R. T.C. Nature. PubMed Scopus Google the Scheller R.H. Full Text Full Text PDF PubMed Scopus Google Scholar), a for to trafficking evolutionary multiple sequence of the VAMP with the evolutionary with the the the in the The between two proteins is to their evolutionary for the are in proteins identified in the of the in the multiple sequence in the is in the of these families of are the of the the is to be the to the membrane 13 and is with of the protein for formation and for membrane between the in are to be responsible for the specificity of between we have that several novel VAMP and syntaxin are in mammalian an of expression and is to understand the full of these families and the specificity of the between many SNARE are in the it be to understand the full repertoire of these molecules in mammalian further of their and it be to understand the the of membrane compartments in mammalian cells. The distribution and restriction of molecules to membrane compartments is an essential process of eukaryotic cells. Distinct organelles of the secretory pathway are synthesized and maintained by budding of transport vesicles from a donor compartment followed by fusion of these vesicles with an acceptor membrane (1Palade G. Science. 1975; 189: 347-358Crossref PubMed Scopus (2322) Google Scholar). The molecular mechanisms responsible for vesicle biogenesis, protein sorting, and membrane fusion are not yet fully understood. While yeast genetics,in vitro biochemistry, and studies of synaptic vesicles have identified many of the components essential for these processes (2Rothman J.E. Nature. 1994; 372: 55-63Crossref PubMed Scopus (1995) Google Scholar, 3Bennett M.K. Scheller R.H. Annu. Rev. Biochem. 1994; 63: 63-100Crossref PubMed Scopus (233) Google Scholar, 4Jahn R. Südhof T.C. Annu. Rev. Neurosci. 1994; 17: 219-246Crossref PubMed Scopus (335) Google Scholar), the full repertoire of important proteins and their mechanisms of action are yet to be determined. One particularly interesting issue is how a vesicle loaded with specific cargo recognizes the appropriate target. It is becoming clear that several independent mechanisms contribute to the specificity of vesicle trafficking, and it is the sum of these multiple layers of specificity that results in a process with high fidelity (5Scheller R.H. Neuron. 1995; 14: 893-897Abstract Full Text PDF PubMed Scopus (196) Google Scholar). vesicle-target membrane recognition event mediated by interaction of integral membrane proteins of the vesicle (v-SNAREs) 1The abbreviations used are: v-SNARE, SNARE on vesicle; ER, endoplasmic reticulum; EST, expressed sequence tag; lgp120, lysosomal glycoprotein of 120 kDa; NRK, normal rat kidney; PCR, polymerase chain reaction; SNAP-25, synaptosome-associated protein of 25 kDa, SNARE, soluble N-ethylmaleimide-sensitive factor-attachment protein receptor; TGN, trans-Golgi network; t-SNARE, SNARE on target membrane; VAMP, vesicle-associated membrane protein; bp, base pair(s); kb, kilobase(s). 1The abbreviations used are: v-SNARE, SNARE on vesicle; ER, endoplasmic reticulum; EST, expressed sequence tag; lgp120, lysosomal glycoprotein of 120 kDa; NRK, normal rat kidney; PCR, polymerase chain reaction; SNAP-25, synaptosome-associated protein of 25 kDa, SNARE, soluble N-ethylmaleimide-sensitive factor-attachment protein receptor; TGN, trans-Golgi network; t-SNARE, SNARE on target membrane; VAMP, vesicle-associated membrane protein; bp, base pair(s); kb, kilobase(s). and target (t-SNAREs) membranes represents one layer of targeting specificity, acting at the final step of membrane fusion (6Bennett M.K. Garcia-Arraras J.E. Elferink L.A. Peterson K. Fleming A.M. Hazuka C.D. Scheller R.H. Full Text PDF PubMed Scopus Google Scholar, J.E. Nature. PubMed Scopus Google Scholar). process in the mammalian formation of a between the v-SNARE, or and the syntaxin and is to a membrane recognition and fusion of the lipid T.C. Nature. 1995; PubMed Scopus Google Scholar, Scheller R.H. Neuron. Full Text Full Text PDF PubMed Scopus Google Scholar). proteins have to be of gene families that membrane compartments (6Bennett M.K. Garcia-Arraras J.E. Elferink L.A. Peterson K. Fleming A.M. Hazuka C.D. Scheller R.H. Full Text PDF PubMed Scopus Google Scholar). syntaxin in yeast have to the G. 1994; PubMed Scopus Google Scholar), PubMed Scopus Google Scholar), Nature. PubMed Scopus Google Scholar), and the membrane and M.K. PubMed Scopus Google Scholar). In the SNAREs present on yeast have and support the that a and a are on membranes for target recognition and membrane fusion Nature. PubMed Scopus Google Scholar). these studies that of the syntaxin and VAMP families define membrane compartments and that specific of these proteins represents a of the specificity of vesicle studies to have to that not vesicle trafficking a distinct the sequence of the yeast the syntaxin and VAMP that be by sequence have the and multiple and of to yeast the of are present in the yeast a of the base of mammalian expressed sequence proposed the of at mammalian Scheller R.H. Nature. PubMed Scopus Google Scholar). In order to fully understand the of membrane compartments in mammalian it to further the of SNARE we have characterized seven new mammalian proteins that we to be SNAREs important in membrane While of the new SNAREs are are enriched in specific an for trafficking in cells. The proteins are to the and a role in membrane trafficking to and from these of identified from the from and of with the yeast sequence PubMed Scopus Google Scholar). distinct sets of The with the sequence The with an of however, it an to at a is from bp, base are from and are from an of of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we a brain and used to a sequence the brain a for the polymerase chain The by a and used to from a rat brain and overlapping The an syntaxin distribution and membrane of syntaxin 13 Scheller R.H. Full Text Full Text PDF PubMed Scopus Google of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we a of that it an for the protein syntaxin of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we a of that it a for the protein VAMP of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we an of that it a for the protein VAMP of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we used in a with a rat The the eukaryotic expression and and and 13 by with with appropriate restriction The the VAMP and and or mammalian expression the by syntaxin 13 a to of syntaxin and used for at The specificity of the by the of to the in not used at a receptor at a of at and at and multiple from with with used for syntaxin used for VAMP and VAMP and a rat used for VAMP for in for at and for at in at high in at a and maintained PubMed Scopus Google Scholar). rat the with and Scheller R.H. Full Text Full Text PDF PubMed Scopus Google sequence and protein the of G. Scholar). the PubMed Google Scholar). of identified from the from and of with the yeast sequence PubMed Scopus Google Scholar). distinct sets of The with the sequence The with an of however, it an to at a is from bp, base are from and are from an of of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we a brain and used to a sequence the brain a for the polymerase chain The by a and used to from a rat brain and overlapping The an syntaxin distribution and membrane of syntaxin 13 Scheller R.H. Full Text Full Text PDF PubMed Scopus Google of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we a of that it an for the protein syntaxin of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we a of that it a for the protein VAMP of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we an of that it a for the protein VAMP of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we used in a with a rat The the eukaryotic expression identified from the from and of with the yeast sequence PubMed Scopus Google Scholar). distinct sets of The with the sequence The with an of however, it an to at a is from bp, base are from and are from an of of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we a brain and used to a sequence the brain a for the polymerase chain The by a and used to from a rat brain and overlapping The an syntaxin distribution and membrane of syntaxin 13 Scheller R.H. Full Text Full Text PDF PubMed Scopus Google of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we a of that it an for the protein syntaxin of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we a of that it a for the protein VAMP of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we an of that it a for the protein VAMP of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we used in a with a rat The the eukaryotic expression and of with the yeast sequence PubMed Scopus Google Scholar). distinct sets of The with the sequence The with an of however, it an to at a is from bp, base are from and are from an of The of with the yeast sequence PubMed Scopus Google Scholar). distinct sets of The with the sequence The with an of however, it an to at a is from bp, base are from and are from an of of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we a brain and used to a sequence the brain a for the polymerase chain The by a and used to from a rat brain and overlapping The an syntaxin distribution and membrane of syntaxin 13 Scheller R.H. Full Text Full Text PDF PubMed Scopus Google Scholar). of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we a brain and used to a sequence the brain a for the polymerase chain The by a and used to from a rat brain and overlapping The an syntaxin distribution and membrane of syntaxin 13 Scheller R.H. Full Text Full Text PDF PubMed Scopus Google Scholar). of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we a of that it an for the protein syntaxin of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we a of that it an for the protein syntaxin VAMP of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we a of that it a for the protein VAMP of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we a of that it a for the protein VAMP VAMP of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we an of that it a for the protein VAMP of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we an of that it a for the protein VAMP VAMP of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we used in a with a rat The the eukaryotic expression of the base Scheller R.H. Nature. PubMed Scopus Google Scholar), we used in a with a rat The the eukaryotic expression and and and 13 by with with appropriate restriction The the VAMP and and or mammalian expression the by and and and 13 by with with appropriate restriction The the VAMP and and or mammalian expression the by syntaxin 13 a to of syntaxin and used for at The specificity of the by the of to the in not used at a receptor at a of at and at syntaxin 13 a to of syntaxin and used for at The specificity of the by the of to the in not used at a receptor at a of at and at and multiple from with with used for syntaxin used for VAMP and VAMP and a rat used for VAMP for in for at and for at in at high in at a and multiple from with with used for syntaxin used for VAMP and VAMP and a rat used for VAMP for in for at and for at in at high in at a and maintained PubMed Scopus Google Scholar). rat the with and Scheller R.H. Full Text Full Text PDF PubMed Scopus Google Scholar). and maintained PubMed Scopus Google Scholar). rat the with and Scheller R.H. Full Text Full Text PDF PubMed Scopus Google Scholar). sequence and protein the of G. Scholar). the PubMed Google Scholar). sequence and protein the of G. Scholar). the PubMed Google Scholar). that or and syntaxin with to a that membranes or in the fusion of membranes Scheller R.H. Neuron. Full Text Full Text PDF PubMed Scopus Google Scholar, R. R. J.E. Full Text Full Text PDF PubMed Scopus Google Scholar). complexes of syntaxin and VAMP have for to and to trafficking Scheller R.H. Full Text Full Text PDF PubMed Scopus Google Scholar, Scheller R.H. PubMed Scopus Google Scholar). The formation of complexes between of these families is specific sets of proteins Scheller R.H. Full Text Full Text PDF PubMed Scopus Google Scholar). it is clear that mechanisms play a role in the transport of vesicles to target specific SNARE is for appropriate membrane rise to the that the of SNARE proteins of the VAMP and syntaxin families define sets of membranes that have the to with on the of the proteins to SNARE protein is a event membrane fusion the of VAMP and syntaxin to the vesicle or target membranes In we define the of novel mammalian SNARE proteins through the of have used and a of SNARE proteins Scheller R.H. Full Text Full Text PDF PubMed Scopus Google Scholar). in the it for to base on that of the the of to we have used to the of the Golgi, syntaxin to the receptor to and to While of the by these is in the to one of the of the specific patterns a on the proteins characterized in are in the a of organelles are studies be to define the membrane compartments by of the in that are trafficking proteins and between donor and acceptor membranes. While studies the of the at the these SNAREs are interesting is VAMP that protein with the lysosomal protein the trafficking VAMP is with from to VAMP be an present at on transport vesicles to the with a high on the VAMP be a present at on vesicles to membrane It is that VAMP a vesicle receptor for are of the of and be Scheller R.H. PubMed Scopus Google Scholar).A of the between and is becoming on the sequence are at of the mammalian syntaxin gene two are to The the syntaxin syntaxin to the membrane and syntaxin to the and 13 to The syntaxin to the TGN, and Scheller R.H. PubMed Scopus Google Scholar). the mammalian are to be that not are the of one that in the and proteins have one gene that to mediate the of membrane in these to have fusion processes the of and is in fusion a of fusion through Nature. PubMed Scopus Google a the or a of proposed a evolutionary The of seven the and and R. T.C. Nature. PubMed Scopus Google the Scheller R.H. Full Text Full Text PDF PubMed Scopus Google Scholar), a for to trafficking of these families of are the of the the is to be the to the membrane 13 and is with of the protein for formation and for membrane between the in are to be responsible for the specificity of between we have that several novel VAMP and syntaxin are in mammalian an of expression and is to understand the full of these families and the specificity of the between many SNARE are in the it be to understand the full repertoire of these molecules in mammalian further of their and it be to understand the the of membrane compartments in mammalian cells. that or and syntaxin with to a that membranes or in the fusion of membranes Scheller R.H. Neuron. Full Text Full Text PDF PubMed Scopus Google Scholar, R. R. J.E. Full Text Full Text PDF PubMed Scopus Google Scholar). complexes of syntaxin and VAMP have for to and to trafficking Scheller R.H. Full Text Full Text PDF PubMed Scopus Google Scholar, Scheller R.H. PubMed Scopus Google Scholar). The formation of complexes between of these families is specific sets of proteins Scheller R.H. Full Text Full Text PDF PubMed Scopus Google Scholar). it is clear that mechanisms play a role in the transport of vesicles to target specific SNARE is for appropriate membrane rise to the that the of SNARE proteins of the VAMP and syntaxin families define sets of membranes that have the to with on the of the proteins to SNARE protein is a event membrane fusion the of VAMP and syntaxin to the vesicle or target membranes In we define the of novel mammalian SNARE proteins through the of have used and a of SNARE proteins Scheller R.H. Full Text Full Text PDF PubMed Scopus Google Scholar). in the it for to base on that of the the of to we have used to the of the Golgi, syntaxin to the receptor to and to While of the by these is in the to one of the of the specific patterns a on the proteins characterized in are in the a of organelles are studies be to define the membrane compartments by of the in that are trafficking proteins and between donor and acceptor membranes. While studies the of the at the these SNAREs are interesting is VAMP that protein with the lysosomal protein the trafficking VAMP is with from to VAMP be an present at on transport vesicles to the with a high on the VAMP be a present at on vesicles to membrane It is that VAMP a vesicle receptor for are of the of and be Scheller R.H. PubMed Scopus Google Scholar). of the between and is becoming on the sequence are at of the mammalian syntaxin gene two are to The the syntaxin syntaxin to the membrane and syntaxin to the and 13 to The syntaxin to the TGN, and Scheller R.H. PubMed Scopus Google Scholar). the mammalian are to be that not are the of one that in the and proteins have one gene that to mediate the of membrane in these to have fusion processes the of and is in fusion a of fusion through Nature. PubMed Scopus Google Scholar). The a the or a of proposed a evolutionary The of seven the and and R. T.C. Nature. PubMed Scopus Google the Scheller R.H. Full Text Full Text PDF PubMed Scopus Google Scholar), a for to trafficking of these families of are the of the the is to be the to the membrane 13 and is with of the protein for formation and for membrane between the in are to be responsible for the specificity of between we have that several novel VAMP and syntaxin are in mammalian an of expression and is to understand the full of these families and the specificity of the between many SNARE are in the it be to understand the full repertoire of these molecules in mammalian further of their and it be to understand the the of membrane compartments in mammalian cells. Peterson for for the syntaxin for and Hazuka for