Biosynthesis and secretion of insect lipoprotein: involvement of furin in cleavage of the apoB homolog, apolipophorin-II/I

Abstract

The biosynthesis of neutral fat-transporting lipoproteins involves the lipidation of their nonexchangeable apolipoprotein. In contrast to its mammalian homolog apolipoprotein B, however, insect apolipophorin-II/I (apoLp-II/I) is cleaved posttranslationally at a consensus substrate sequence for furin, resulting in the appearance of two apolipoproteins in insect lipoprotein. To characterize the cleavage process, a truncated cDNA encoding the N-terminal 38% of Locusta migratoria apoLp-II/I, including the cleavage site, was expressed in insect Sf9 cells. This resulted in the secretion of correctly processed apoLp-II and truncated apoLp-I. The cleavage could be impaired by the furin inhibitor decanoyl-Arg-Val-Lys-Arg-chloromethyl ketone (decRVKRcmk) as well as by mutagenesis of the consensus substrate sequence for furin, as indicated by the secretion of uncleaved apoLp-II/I-38. Treatment of L. migratoria fat body, the physiological site of lipoprotein biosynthesis, with decRVKRcmk similarly resulted in the secretion of uncleaved apoLp-II/I, which was integrated in lipoprotein particles of buoyant density identical to wild-type high density lipophorin (HDLp).These results show that apoLp-II/I is posttranslationally cleaved by an insect furin and that biosynthesis and secretion of HDLp can occur independent of this processing step. Structure modeling indicates that the cleavage of apoLp-II/I represents a molecular adaptation in homologous apolipoprotein structures. We propose that cleavage enables specific features of insect lipoproteins, such as low density lipoprotein formation, endocytic recycling, and involvement in coagulation. The biosynthesis of neutral fat-transporting lipoproteins involves the lipidation of their nonexchangeable apolipoprotein. In contrast to its mammalian homolog apolipoprotein B, however, insect apolipophorin-II/I (apoLp-II/I) is cleaved posttranslationally at a consensus substrate sequence for furin, resulting in the appearance of two apolipoproteins in insect lipoprotein. To characterize the cleavage process, a truncated cDNA encoding the N-terminal 38% of Locusta migratoria apoLp-II/I, including the cleavage site, was expressed in insect Sf9 cells. This resulted in the secretion of correctly processed apoLp-II and truncated apoLp-I. The cleavage could be impaired by the furin inhibitor decanoyl-Arg-Val-Lys-Arg-chloromethyl ketone (decRVKRcmk) as well as by mutagenesis of the consensus substrate sequence for furin, as indicated by the secretion of uncleaved apoLp-II/I-38. Treatment of L. migratoria fat body, the physiological site of lipoprotein biosynthesis, with decRVKRcmk similarly resulted in the secretion of uncleaved apoLp-II/I, which was integrated in lipoprotein particles of buoyant density identical to wild-type high density lipophorin (HDLp). These results show that apoLp-II/I is posttranslationally cleaved by an insect furin and that biosynthesis and secretion of HDLp can occur independent of this processing step. Structure modeling indicates that the cleavage of apoLp-II/I represents a molecular adaptation in homologous apolipoprotein structures. We propose that cleavage enables specific features of insect lipoproteins, such as low density lipoprotein formation, endocytic recycling, and involvement in coagulation. Lipoproteins mediate most of the lipid transport in the circulation of animals. In mammals, a single protein component, the nonexchangeable apolipoprotein B (apoB), provides the structural basis for the biosynthesis of neutral fat-transporting lipoproteins (1Shelness G.S. Sellers J.A. Very-low-density lipoprotein assembly and secretion.Curr. Opin. Lipidol. 2001; 12: 151-157Crossref PubMed Scopus (235) Google Scholar, 2Mahmood Hussain M. Kedees M.H. Singh K. Athar H. Jamali N.Z.Z. Signposts in the assembly of chylomicrons.Front. Biosci. 2001; 6: D320-D331Crossref PubMed Google Scholar). Interestingly, the major lipoprotein of insects, lipophorin, contains two structural apolipoproteins, because the insect apoB homolog (3Babin P.J. Bogerd J. Kooiman F.P. Van Marrewijk W.J.A. Van der Horst D.J.J. Apolipophorin II/I, apolipoprotein B, vitellogenin, and microsomal triglyceride transfer protein genes are derived from a common ancestor.J. Mol. Evol. 1999; 49: 150-160Crossref PubMed Scopus (178) Google Scholar, 4Mann C.J. Anderson T.A. Read J. Chester S.A. Harrison G.B. Kochl S. Ritchie P.J. Bradbury P. Hussain F.S. Amey J. Vanloo B. Rosseneu M. Infante R. Hancock J.M. Levitt D.G. Banaszak L.J. Scott J. Shoulders C.C.C. The structure of vitellogenin provides a molecular model for the assembly and secretion of atherogenic lipoproteins.J. Mol. Biol. 1999; 285: 391-408Crossref PubMed Scopus (170) Google Scholar), the precursor apolipophorin-II/I (apoLp-II/I), is cleaved during lipoprotein biosynthesis by the fat body (5Van der Horst D.J. Weers P.M.M. Van Marrewijk W.J.A. Lipoproteins and lipid transport.in: Stanley-Samuelson D.W. Nelson D.R. Insect Lipids: Chemistry, Biochemistry, and Biology. University of Nebraska Press, Lincoln, NE1993: 1-24Google Scholar, 6Weers P.M.M. Van Marrewijk W.J.A. Beenakkers A.M.T. Van der Horst D.J.J. Biosynthesis of locust lipophorin. Apolipophorins I and II originate from a common precursor.J. Biol. Chem. 1993; 268: 4300-4303Abstract Full Text PDF PubMed Google Scholar). Cleavage of apoLp-II/I can be related to the activity of furin, a member of the proprotein convertase (PC) family of subtilisin-like serine endoproteases that is mainly active in the trans-Golgi network (7Taylor N.A. Van de Ven W.J.M. Creemers J.W.M. Curbing activation: proprotein convertases in homeostasis and pathology.FASEB J. 2003; 17: 1215-1227Crossref PubMed Scopus (191) Google Scholar). The preferred consensus substrate sequence for furin, R-X-K/R-R, is present in all apoLp-II/I sequences characterized to date (8Kutty R.K. Kutty G. Kambadur R. Duncan T. Koonin E.V. Rodriguez I.R. Odenwald W.F. Wiggert B.B. Molecular characterization and developmental expression of a retinoid- and fatty acid-binding glycoprotein from Drosophila. A putative lipophorin.J. Biol. Chem. 1996; 271: 20641-20649Abstract Full Text Full Text PDF PubMed Scopus Google Scholar, K. The precursor protein of the structural apolipoproteins of cDNA and Mol. Biol. 1996; PubMed Scopus Google Scholar, J. P.J. Kooiman F.P. M. Van Marrewijk W.J.A. Van der Horst D.J.J. Molecular characterization and expression in the of the precursor from Locusta PubMed Scopus Google Scholar, R. D.R. P. J.M. R. B. M. P. H. de J. R. M. S. K. M. M. L. P. R. J. J.A. S. J. R. K. H. J. R. J. P. B. J. M. M. H. S. M. S. P. J. The sequence of the PubMed Scopus Google Scholar). In with the activity of furin, Locusta migratoria apoLp-II/I to be cleaved of its furin substrate as indicated by the N-terminal sequence of J. P.J. Kooiman F.P. M. Van Marrewijk W.J.A. Van der Horst D.J.J. Molecular characterization and expression in the of the precursor from Locusta PubMed Scopus Google Scholar). The furin cleavage site in insect apoLp-II/I is in the lipid transfer which the N-terminal of apoLp-II/I that sequence to that of the microsomal triglyceride transfer protein and vitellogenin (3Babin P.J. Bogerd J. Kooiman F.P. Van Marrewijk W.J.A. Van der Horst D.J.J. Apolipophorin II/I, apolipoprotein B, vitellogenin, and microsomal triglyceride transfer protein genes are derived from a common ancestor.J. Mol. Evol. 1999; 49: 150-160Crossref PubMed Scopus (178) Google Scholar, 4Mann C.J. Anderson T.A. Read J. Chester S.A. Harrison G.B. Kochl S. Ritchie P.J. Bradbury P. Hussain F.S. Amey J. Vanloo B. Rosseneu M. Infante R. Hancock J.M. Levitt D.G. Banaszak L.J. Scott J. Shoulders C.C.C. The structure of vitellogenin provides a molecular model for the assembly and secretion of atherogenic lipoproteins.J. Mol. Biol. 1999; 285: 391-408Crossref PubMed Scopus (170) Google Scholar). In this is for lipoprotein The the of apoB and that of the enables the assembly of lipoproteins (1Shelness G.S. Sellers J.A. Very-low-density lipoprotein assembly and secretion.Curr. Opin. Lipidol. 2001; 12: 151-157Crossref PubMed Scopus (235) Google Scholar, 2Mahmood Hussain M. Kedees M.H. Singh K. Athar H. Jamali N.Z.Z. Signposts in the assembly of chylomicrons.Front. Biosci. 2001; 6: D320-D331Crossref PubMed Google Scholar). The apoB and apoLp-II/I, as well as the of an in J.A. L. Athar H. Hussain M. G.S. A microsomal triglyceride transfer protein homolog the assembly and secretion of apolipoprotein B. for and insect transport and Biol. Chem. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar), that the of apoLp-II/I enables lipoprotein biosynthesis in as that the cleavage of apoLp-II/I in the in the biosynthesis and secretion of insect lipoprotein. In the present characterize the involvement of insect furin in the cleavage of L. migratoria apoLp-II/I and the of this to insect lipoprotein biosynthesis and To this apoLp-II/I cleavage was in a insect expression for truncated apoLp-II/I as well as in the locust fat body, the insect that apoLp-II/I and its cleavage and in the of a high density lipophorin P.M.M. Van Marrewijk W.J.A. Beenakkers A.M.T. Van der Horst D.J.J. Biosynthesis of locust lipophorin. Apolipophorins I and II originate from a common precursor.J. Biol. Chem. 1993; 268: 4300-4303Abstract Full Text PDF PubMed Google Scholar, P.M.M. Van der Horst D.J. Van Marrewijk W.J.A. Van M. Van J.M. Beenakkers A.M.T. Biosynthesis and secretion of insect Full Text PDF PubMed Google Scholar). The results that L. migratoria apoLp-II/I is cleaved by an insect apoLp-II/I could be and a high density lipoprotein. We that cleavage of apoLp-II/I is for the biosynthesis and secretion of lipophorin. this a molecular adaptation specific features of insect of apoLp-II/I to the homologous the structure and an apoB indicated the of the cleavage site in the apoLp-II/I and putative for apoLp-II/I cleavage are and J. P.J. Kooiman F.P. M. Van Marrewijk W.J.A. Van der Horst D.J.J. Molecular characterization and expression in the of the precursor from Locusta PubMed Scopus Google Scholar, J. T. Molecular A Press, to an expression for L. migratoria The was by the cDNA from cDNA J. P.J. Kooiman F.P. M. Van Marrewijk W.J.A. Van der Horst D.J.J. Molecular characterization and expression in the of the precursor from Locusta PubMed Scopus Google this was to and The of this encoding apoLp-II/I, was the insect expression the a a site, was of the to of the of the apoLp-II/I cDNA sequence with the and sequences of the are and In the apoLp-II/I cDNA from cDNA J. P.J. Kooiman F.P. M. Van Marrewijk W.J.A. Van der Horst D.J.J. Molecular characterization and expression in the of the precursor from Locusta PubMed Scopus Google was the and to In a the from was the and II of the of this that the resulting in the apoLp-II/I in at the with a as well as a the J. P.J. Kooiman F.P. M. Van Marrewijk W.J.A. Van der Horst D.J.J. Molecular characterization and expression in the of the precursor from Locusta PubMed Scopus Google Scholar), this apoLp-II/I to 38% of the precursor protein and is to as apoLp-II/I-38. The at the and the of the active site in PubMed Scopus Google the furin cleavage site in the to the the in with their to be are to be are in The and in a of at at and at with of the as the the to and The of in was by Sf9 in in in at in a and with the wild-type and to the and at in with to with the furin inhibitor decanoyl-Arg-Val-Lys-Arg-chloromethyl ketone by including the inhibitor its in for and from and by and for and cleavage by L. migratoria in at a of and a of with from in two the and in in a at for at in of of fat to of with of with decRVKRcmk an of its in the for apoLp-II/I and cleavage by The buoyant density of apoLp-II/I and cleavage was by the of and fat body to density P.M.M. Van der Horst D.J. Van Marrewijk W.J.A. Van M. Van J.M. Beenakkers A.M.T. Biosynthesis and secretion of insect Full Text PDF PubMed Google Scholar). of for the of apoLp-II/I and cleavage by the by a Molecular with from by the of to a of and at in that was by the of to by for for fat body as a protein molecular and wild-type L. migratoria HDLp P.M.M. Van Marrewijk W.J.A. Beenakkers A.M.T. Van der Horst D.J.J. Biosynthesis of locust lipophorin. Apolipophorins I and II originate from a common precursor.J. Biol. Chem. 1993; 268: 4300-4303Abstract Full Text PDF PubMed Google was as a to a and was as Van der Horst D.J. Insect lipoprotein a that is by the insect PubMed Scopus Google Scholar). Van der Horst D.J. H. Beenakkers A.M.T. specific for of from the Insect 6: Scopus Google Scholar), and in the and which to the of apoLp-II and the of the was as a The L. migratoria apoLp-II/I sequence was to homologous and the from the for D.J. Mol. Biol. PubMed Scopus Google Scholar). The for the The most to sequences from apoLp-II/I, and vitellogenin, including the The D.G. the of sequence sequence and PubMed Scopus Google was to the homologous N-terminal of and L. migratoria This was to the structural model of the the of locust apoLp-II/I the protein by of Mol. Biol. 1993; PubMed Scopus Google Scholar), the structure of Banaszak L.J. in PubMed Scopus Google and an all model for apoB M. of lipoprotein particles structural model for the lipoprotein J. In Scholar). To and to and the apoLp-II/I model was to of the from A of the model was by the and the an for protein PubMed Scopus Google Scholar). To the sequence of apoLp-II/I that an apoLp-II/I was expressed in the insect Sf9 which a furin homolog M. and characterization of a subtilisin-like Chem. PubMed Scopus Google Scholar). The the N-terminal 38% of apoLp-II/I This the the sequence for apoLp-II with the consensus substrate sequence for furin, by N-terminal from to the and a to as of Sf9 with this resulted in the secretion of apoLp-II and cleavage the as by of is indicated by the single with and and as well as the at to the molecular of The of the of its in of apoLp-II is indicated by with apoLp-II and and which results in a single at This protein to to the apoLp-II from L. migratoria HDLp This indicates that apoLp-II is similarly as wild-type with resulted in a single apoLp-II with a molecular of which is to that for wild-type locust apoLp-II P.M.M. Van Marrewijk W.J.A. Beenakkers A.M.T. Van der Horst D.J.J. Biosynthesis of locust lipophorin. Apolipophorins I and II originate from a common precursor.J. Biol. Chem. 1993; 268: 4300-4303Abstract Full Text PDF PubMed Google Scholar). the of and wild-type apoLp-II indicates that the cleavage of identical to that in fat body P.M.M. Van Marrewijk W.J.A. Beenakkers A.M.T. Van der Horst D.J.J. Biosynthesis of locust lipophorin. Apolipophorins I and II originate from a common precursor.J. Biol. Chem. 1993; 268: 4300-4303Abstract Full Text PDF PubMed Google Scholar, J. P.J. Kooiman F.P. M. Van Marrewijk W.J.A. Van der Horst D.J.J. Molecular characterization and expression in the of the precursor from Locusta PubMed Scopus Google Scholar). of a the N-terminal of apoLp-II/I in Sf9 and in resulted in the secretion of the two apoLp-II/I cleavage is cleaved at the site as apoLp-II/I in L. The and of the sequences that the cleavage site and apoLp-II and and In of the in the putative furin cleavage site the results in the secretion of uncleaved as by the single with and at to the molecular of apoLp-II and The of apoLp-II/I to the In the of cleavage was Sf9 apoLp-II and at the consensus substrate sequence for furin, to apoLp-II/I in locust fat These results the of this expression to characterize apoLp-II/I The cleavage apoLp-II and characterized for and The of apoLp-II with that cleavage can a density the cleavage apoLp-II and in the with and as was uncleaved These results that the are the for apoLp-II/I cleavage in lipidation was in L. migratoria fat body the present expression was to characterize apoLp-II/I is a that a of including furin K. L. G. G. a for as an PubMed Scopus Google and the furin homolog characterized from the insect Sf9 M. and characterization of a subtilisin-like Chem. PubMed Scopus Google Scholar). of Sf9 with the with of decRVKRcmk resulted in the secretion of uncleaved secretion of apoLp-II and was and as by the of and the of cleavage to be for to at a of The to decRVKRcmk indicates the involvement of a in the cleavage of To for the involvement of in a was at which is to by at the sequence for cleavage of by PubMed Google Scholar, Creemers J.W.M. T.A. Van de Ven W.J.M. proprotein processing involvement of in the substrate PubMed Scopus Google Scholar, S. R. R. The structure of the proprotein processing furin its Biol. 2003; PubMed Scopus Google Scholar). by of from Sf9 of at the to cleavage the involvement of a in the cleavage of To the sequence that the cleavage of apoLp-II/I, the in the furin consensus substrate sequence of to neutral at the to cleavage of In of the cleavage site at the to to cleavage of the cleavage at cleavage for mammalian sequence for cleavage of by PubMed Google Scholar, D.J. T. processing by PubMed Scopus Google Scholar). of cleavage the secretion of truncated apoLp-II/I by the expression These results that apoLp-II/I cleavage in Sf9 the of the preferred consensus substrate sequence for furin, R-X-K/R-R, in This indicates the involvement of an insect furin in apoLp-II/I To the involvement of an insect furin in lipophorin biosynthesis, and to the of cleavage for secretion in a physiological fat body from was in with the of of HDLp that to fat body was in to To apoLp-II/I, to density and the resulting for by with fat body with decRVKRcmk resulted in the appearance of an of high molecular and a in the putative in with an buoyant density of identical to the density for wild-type HDLp P.M.M. Van der Horst D.J. Van Marrewijk W.J.A. Van M. Van J.M. Beenakkers A.M.T. Biosynthesis and secretion of insect Full Text PDF PubMed Google Scholar). The of the in as apoLp-II/I and was by with apoLp-II could be its in the as apoLp-II/I and The of apoLp-II/I cleavage to decRVKRcmk with was in the fat body, with the expression with This of decRVKRcmk the fat body, as the of this inhibitor to at the of the lipid in this fat body can uncleaved apoLp-II/I with a buoyant density identical to wild-type indicates that this apoLp-II/I particles with a molecular identical to wild-type HDLp results that fat body can uncleaved apoLp-II/I that integrated in a high density lipoprotein to wild-type the biosynthesis as well as secretion of insect lipoprotein can occur of apoLp-II/I The of uncleaved apoLp-II/I to a lipoprotein the structural insect and mammalian lipoproteins in the of its To a of the structural of L. migratoria apoLp-II/I was to the homologous the structure Banaszak L.J. in PubMed Scopus Google and an apoB model M. of lipoprotein particles structural model for the lipoprotein J. In Scholar). The apoLp-II/I model and the This apoLp-II/I sequence can a structure to that of the and apoB as indicated by the of and and an structure The and to a putative lipid and are by the The is resulting in a which is the putative lipid The apoLp-II/I cleavage site, and was in an that two of the at the of the putative lipid This could be The sequence was in the structure of Banaszak L.J. in PubMed Scopus Google Scholar), which is of structural in this of and in the of apoLp-II/I to the present apoLp-II the the and most of the of two from the the and is well that insect lipoproteins two apolipoproteins, and that are derived from their common precursor protein apoLp-II/I P.M.M. Van Marrewijk W.J.A. Beenakkers A.M.T. Van der Horst D.J.J. Biosynthesis of locust lipophorin. Apolipophorins I and II originate from a common precursor.J. Biol. Chem. 1993; 268: 4300-4303Abstract Full Text PDF PubMed Google Scholar, R.K. Kutty G. Kambadur R. Duncan T. Koonin E.V. Rodriguez I.R. Odenwald W.F. Wiggert B.B. Molecular characterization and developmental expression of a retinoid- and fatty acid-binding glycoprotein from Drosophila. A putative lipophorin.J. Biol. Chem. 1996; 271: 20641-20649Abstract Full Text Full Text PDF PubMed Scopus Google Scholar, K. The precursor protein of the structural apolipoproteins of cDNA and Mol. Biol. 1996; PubMed Scopus Google Scholar, J. P.J. Kooiman F.P. M. Van Marrewijk W.J.A. Van der Horst D.J.J. Molecular characterization and expression in the of the precursor from Locusta PubMed Scopus Google Scholar, R. D.R. P. J.M. R. B. M. P. H. de J. R. M. S. K. M. M. L. P. R. J. J.A. S. J. R. K. H. J. R. J. P. B. J. M. M. H. S. M. S. P. J. The sequence of the PubMed Scopus Google Scholar). In the present and characterized the cleavage site in L. migratoria apoLp-II/I an insect expression of Sf9 and that its cleavage involves an insect locust fat body can uncleaved apoLp-II/I in the of a lipoprotein with a buoyant density and molecular identical to wild-type that cleavage of apoLp-II/I by insect furin is for the biosynthesis the secretion of this insect lipoprotein. The involvement of an insect furin in the cleavage of L. migratoria apoLp-II/I is indicated by apoLp-II/I cleavage in the Sf9 expression and locust fat body can be by which K. L. G. G. a for as an PubMed Scopus Google Scholar), including the furin homolog characterized from the insect Sf9 M. and characterization of a subtilisin-like Chem. PubMed Scopus Google Scholar). cleavage is by of the at the to a the of a at the substrate of this is to the substrate sequence for cleavage of by PubMed Google Scholar, Creemers J.W.M. T.A. Van de Ven W.J.M. proprotein processing involvement of in the substrate PubMed Scopus Google Scholar, S. R. R. The structure of the proprotein processing furin its Biol. 2003; PubMed Scopus Google Scholar). processing an furin consensus substrate sequence with at and of of neutral of results in the secretion of uncleaved apoLp-II/I, cleavage occur in the and furin is to with at sequences that the preferred substrate sequence sequence for cleavage of by PubMed Google Scholar, D.J. T. processing by PubMed Scopus Google Scholar). the cleavage in and from activity of furin at results cleavage of apoLp-II/I by an insect furin in In cleavage activity and for the and Van de Ven W.J.M. cDNA sequence of a encoding a protein related to the subtilisin-like proprotein processing PubMed Scopus Google Scholar, Creemers J.W.M. M. Van de Ven W.J.M. and expression of a subtilisin-like proprotein processing of with of a Biol. Chem. Full Text PDF PubMed Google Scholar, R. Van de Ven W.J.M. and biosynthesis of the convertases and Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). a furin was from the insect Sf9 M. and characterization of a subtilisin-like Chem. PubMed Scopus Google Scholar). a with activity is present in the fat body of cleavage of by a subtilisin-like 1996; PubMed Scopus Google Scholar). putative furin in L. migratoria fat In Sf9 as well as locust fat body, uncleaved apoLp-II/I could be in as its cleavage The cleavage apoLp-II and to a integrated in a high density in contrast to apoLp-II/I by locust fat body, as in the high density density The lipidation of the is in with the lipidation for apoB (1Shelness G.S. Sellers J.A. Very-low-density lipoprotein assembly and secretion.Curr. Opin. Lipidol. 2001; 12: 151-157Crossref PubMed Scopus (235) Google Scholar, M. of lipoprotein particles structural model for the lipoprotein J. In the of for lipidation in the present expression the of cleavage in the lipidation and secretion of insect lipoprotein was in locust fat decRVKRcmk resulted in the secretion of uncleaved apoLp-II/I that a high density as indicated by its density and molecular identical to wild-type the uncleaved precursor apoLp-II/I can as a single apolipoprotein in the of its mammalian homolog apoLp-II/I can be to a high density of its The lipidation of apoB in the and is posttranslationally in the by with an lipid (1Shelness G.S. Sellers J.A. Very-low-density lipoprotein assembly and secretion.Curr. Opin. Lipidol. 2001; 12: 151-157Crossref PubMed Scopus (235) Google Scholar, 2Mahmood Hussain M. Kedees M.H. Singh K. Athar H. Jamali N.Z.Z. Signposts in the assembly of chylomicrons.Front. Biosci. 2001; 6: D320-D331Crossref PubMed Google Scholar). The lipidation with the lipidation of the lipid in the apoB and the lipid transfer activity of (1Shelness G.S. Sellers J.A. Very-low-density lipoprotein assembly and secretion.Curr. Opin. Lipidol. 2001; 12: 151-157Crossref PubMed Scopus (235) Google Scholar, 2Mahmood Hussain M. Kedees M.H. Singh K. Athar H. Jamali N.Z.Z. Signposts in the assembly of chylomicrons.Front. Biosci. 2001; 6: D320-D331Crossref PubMed Google Scholar). the apoB and apoLp-II/I (3Babin P.J. Bogerd J. Kooiman F.P. Van Marrewijk W.J.A. Van der Horst D.J.J. Apolipophorin II/I, apolipoprotein B, vitellogenin, and microsomal triglyceride transfer protein genes are derived from a common ancestor.J. Mol. Evol. 1999; 49: 150-160Crossref PubMed Scopus (178) Google Scholar, 4Mann C.J. Anderson T.A. Read J. Chester S.A. Harrison G.B. Kochl S. Ritchie P.J. Bradbury P. Hussain F.S. Amey J. Vanloo B. Rosseneu M. Infante R. Hancock J.M. Levitt D.G. Banaszak L.J. Scott J. Shoulders C.C.C. The structure of vitellogenin provides a molecular model for the assembly and secretion of atherogenic lipoproteins.J. Mol. Biol. 1999; 285: 391-408Crossref PubMed Scopus (170) Google as well as the of an insect J.A. L. Athar H. Hussain M. G.S. A microsomal triglyceride transfer protein homolog the assembly and secretion of apolipoprotein B. for and insect transport and Biol. Chem. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar), insect lipoprotein assembly occur in the cleavage by furin is in the mainly in the trans-Golgi network Anderson G. the furin from to and Biol. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). propose that insect lipoprotein biosynthesis by the fat body involves lipidation of apoLp-II/I to a lipoprotein by cleavage of apoLp-II/I and The of cleavage lipidation in the of and and of lipoprotein The uncleaved in apoLp-II/I be to the in as in modeling that the of apoLp-II/I can a putative lipid the cleavage site is in an two in the at the of this In the is to in lipidation as a structure that the of the lipid by to the M. of lipoprotein particles structural model for the lipoprotein J. In Scholar). the lipid of apoB a lipid during lipoprotein are to This for of the lipid by and and the of apoB lipidation M. of lipoprotein particles structural model for the lipoprotein J. In Scholar, M. G. lipoprotein lipid of the lipoprotein Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). The cleavage of apoLp-II/I an structural to the lipid and the of the nonexchangeable for lipidation of the lipoprotein Interestingly, can HDLp to a low density lipophorin during that lipid transport and Van der Horst D.J. transport and its in PubMed Scopus Google Scholar, of lipophorin in lipid transport to the insect Biol. Chem. Full Text PDF PubMed Google Scholar). apoLp-II/I cleavage to the of from The of apoLp-II/I cleavage in all characterized to date the of this processing step. formation, however, apoLp-II/I cleavage insect lipoprotein such as the of lipophorin to as a lipid Van der Horst D.J. transport and its in PubMed Scopus Google and to be endocytic by an insect member of the low density lipoprotein family Van der Horst D.J. 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K. of locust lipophorin during 17: Scopus Google Scholar, R. of locust for lipoprotein In of Lipoproteins with and the The Scholar), and with insect and two molecular for insect involvement in Insect PubMed Scopus Google Scholar). the of apoLp-II from during B. M. major from locust are in and are by a Mol. Biol. PubMed Scopus Google that apoLp-II/I cleavage enables for and apoLp-II in coagulation. Cleavage of the insect apoB homolog apoLp-II/I to be a molecular adaptation homologous and a insect lipoprotein The of apoLp-II/I lipoprotein from fat body a furin inhibitor in the physiological of apoLp-II/I the expression of truncated apoLp-II/I be to of insect lipoprotein assembly and such as lipid in and the of and in and lipoprotein A for apolipoprotein with and with PubMed Scopus Google Scholar), as well as the in insect lipoprotein apoB with a to can high density lipoprotein particles are with and J.A. L. Athar H. Hussain M. G.S. 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