Involvement of Napsin A in the C- and N-terminal Processing of Surfactant Protein B in Type-II Pneumocytes of the Human Lung

Abstract

Surfactant protein B (SP-B) is a critical component of pulmonary surfactant, and a deficiency of active SP-B results in fatal respiratory failure. SP-B is synthesized by type-II pneumocytes as a 42-kDa propeptide (proSP-B), which is posttranslationally processed to an 8-kDa surface-active protein. Napsin A is an aspartic protease expressed in type-II pneumocytes. To characterize the role of napsin A in the processing of proSP-B, we colocalized napsin A and precursors of SP-B as well as SP-B in the Golgi complex, multivesicular, composite, and of type-II pneumocytes in we aspartic protease in as well as type-II pneumocytes and the of by napsin A and in napsin A and and processing of by by an aspartic protease of processing in the and as well as in the of the processing in in type-II pneumocytes. results napsin A is in the and processing of in type-II pneumocytes. Surfactant protein B (SP-B) is a critical component of pulmonary surfactant, and a deficiency of active SP-B results in fatal respiratory failure. SP-B is synthesized by type-II pneumocytes as a 42-kDa propeptide (proSP-B), which is posttranslationally processed to an 8-kDa surface-active protein. Napsin A is an aspartic protease expressed in type-II pneumocytes. To characterize the role of napsin A in the processing of proSP-B, we colocalized napsin A and precursors of SP-B as well as SP-B in the Golgi complex, multivesicular, composite, and of type-II pneumocytes in we aspartic protease in as well as type-II pneumocytes and the of by napsin A and in napsin A and and processing of by by an aspartic protease of processing in the and as well as in the of the processing in in type-II pneumocytes. results napsin A is in the and processing of in type-II pneumocytes. and of pulmonary of of to respiratory of pulmonary is the of the the in the is a of and is and to a by type-II pneumocytes of the protein B (SP-B) protein of protein of and to the of the of as well as the of the in SP-B deficiency in to respiratory in in the SP-B as well as pulmonary in and by an of and SP-B SP-B precursors in by the of in type-II pneumocytes. processing of to a of in SP-B processing of in pulmonary in and is synthesized in type-II pneumocytes as a of to the the processing to SP-B the of the of the by the of the and propeptide processing of the and processing to 8-kDa SP-B is an of the propeptide and of the propeptide processing and the of processing is the of the in the a protease is in the processing of the protein B in type-II and in a aspartic napsin in type-II pneumocytes of the by as well as in of napsin A in the napsin A and a we napsin A the protease in the processing of the role of napsin A in the processing of we the of SP-B and napsin A in by napsin A in and type-II pneumocytes. the by napsin A in and processing by and SP-B precursors in type-II the we and the the of as as the by by and by and in of the and a by of the the to and as in type-II pneumocytes as of in by the of and to the and to in the to protease as pneumocytes by and to of by as by the type-II pneumocytes in of and of the by the in of a SP-B to an the as and a as a and of the to and and the the and the and a the of the expressed protein. protein of and a of of as as the and in to an of to the to a of to the and the by in and by and in in the of the of the to a and the protein and in in the the by napsin A by a of as of and as and a SP-B by and and by of and the of and in a of and in an To to the the in in the the to the of the as in and and as in in the by of a of and in the the of to the of by a in and in to in to a of and to and to the To and the in and in the to the in and by a in and the a of and SP-B and napsin as the napsin A and the SP-B in by a and in we and A as and in a of by a by of the of the and and the and of of to the in and to and the to in the of the Napsin of napsin A in the napsin A by the of the a and in protease and of of and the by the of of a of an in the and of Napsin and of napsin A as an napsin A Napsin A the the propeptide and napsin A and in of Napsin A napsin A in and napsin A as well as in the of napsin A and as well as in the of and the by as in the of in and of the and type-II pneumocytes and by and to to the of the the and of the to the and the of Napsin A of napsin A of napsin and of in a a in of the the by and of by Napsin A of SP-B napsin A as by in and SP-B the the a by and of and the in a and of and the by of a of and by and in a the in and a in of and in a a in of the the of in napsin in type-II pneumocytes. an the as well as a in type-II napsin A in the Golgi and in the napsin A in the and in of the a and the of the and is a the processing in we A and napsin A and napsin A and colocalized in a a and napsin A and SP-B colocalized in multivesicular, composite, and and of napsin A and precursors of SP-B as well as SP-B by napsin A and the propeptide of a of napsin A and precursors of SP-B in a in Napsin A colocalized SP-B in the of and the of Napsin A in and napsin A is synthesized as an and napsin A the and the we napsin A in and in type-II pneumocytes. A in the the of the to napsin A and of the by of the aspartic protease of by Napsin napsin A to in of napsin and by the SP-B and a and the processing of by the of a and of in and in processing by napsin A and and processing and and processing by the SP-B and and the the processing of by napsin A by the of and To the of napsin A and the processing in we in the of the protease the aspartic protease the processing by type-II pneumocytes of and an SP-B and by to and the to and and of Napsin A we the we napsin A and the of the to the in the and the of the by of the in of by napsin to a the and a the napsin the and by as and of the processing the of the by of the of the the and the of and A which by napsin to of by the of napsin A the we processing by the and the as the by napsin A To of in by is by an aspartic protease we an of an of aspartic the processing of by to the of by napsin A to the of the protein a to the napsin A we a of the and of by napsin A and by and to of in To the an and the by in the of napsin A and the of the processing by the of the of the protein by napsin A of by napsin A processing processing processing in a in processing in SP-B precursors in we type-II pneumocytes. type-II and SP-B precursors of and and by to and the to and and of the processing well to of the by napsin A we a protease in the of SP-B precursors we to an of processing by napsin A in type-II pneumocytes we type-II pneumocytes of and SP-B precursors by and and and of the of SP-B well to of the by napsin A of processing in type-II pneumocytes of of in as well as and precursors of SP-B in type-II pneumocytes and and which in and and a role in SP-B is synthesized as a processing is a A of SP-B precursors of SP-B in of and the of precursors of SP-B in and pulmonary a pulmonary to a of processing of A deficiency of the in the processing a a protease to the processing of in type-II pneumocytes by by and in we the aspartic protease napsin which in type-II pneumocytes of the the aspartic protease napsin A is a and SP-B a we napsin precursors of and SP-B in the by the propeptide of precursors of SP-B in the and Golgi in a in we SP-B in multivesicular, composite, and type-II pneumocytes in in Golgi Napsin A to colocalized precursors of SP-B SP-B in Golgi and SP-B and napsin A in which the the of and in and SP-B is the Golgi the and to the and the processing of in the Golgi and napsin A and precursors of SP-B as well as SP-B colocalized in type-II pneumocytes napsin A in the processing of we napsin A is active in type-II pneumocytes in the of napsin A well the in and the processing of by napsin we as well as napsin and in processing the of the protein is to the of the protein and a napsin A processing to processing by an aspartic protease in to we the processing in type-II pneumocytes. the and the of SP-B the propeptide in we a of the of SP-B well to of the in of an processing in type-II which well to the in the processing is the of SP-B in type-II pneumocytes we the napsin A the protein. of the processing the SP-B and of the as well as the of the of the propeptide to the processing the and in the propeptide in an and in the processing by napsin A and in a in the propeptide and the processing of processing is by an by a a and a processing of processing in which in pneumocytes the processing a the of SP-B and the the processing to the in of SP-B in the napsin A and the processing and a processing in type-II pneumocytes of an processing of to an of the role of napsin A in the processing of in to napsin in of of of the in the processing of and in an of and results napsin A is in the processing of in type-II pneumocytes in the of the of napsin A in the and processing of we a of napsin A and precursors of SP-B as well as SP-B in the in type-II pneumocytes. and type-II pneumocytes napsin A napsin A and processing of of processing of in the and propeptide as well as in the of by napsin A in the of the aspartic protease processing of in in type-II pneumocytes the processing of in by napsin A and in type-II pneumocytes of protease processing of is by by a napsin A to SP-B in in the of the and of protease is a the of the and of the processing to napsin A the the pulmonary as is in processing of and of pulmonary of of to respiratory of pulmonary is the of the the in the is a of and is and to a by type-II pneumocytes of the protein B (SP-B) protein of protein of and to the of the of as well as the of the in SP-B deficiency in to respiratory in in the SP-B as well as pulmonary in and by an of and SP-B SP-B precursors in by the of in type-II pneumocytes. processing of to a of in SP-B processing of in pulmonary in and protein B of protein B of SP-B is synthesized in type-II pneumocytes as a of to the the processing to SP-B the of the of the by the of the and propeptide processing of the and processing to 8-kDa SP-B is an of the propeptide and of the propeptide processing and the of processing is the of the in the a protease is in the processing of the protein B in type-II and in a aspartic napsin in type-II pneumocytes of the by as well as in of napsin A in the napsin A and a we napsin A the protease in the processing of To the role of napsin A in the processing of we the of SP-B and napsin A in by napsin A in and type-II pneumocytes. the by napsin A in and processing by and SP-B precursors in type-II pneumocytes. the we and the the of as as the by by and by and in of the and a by of the the to and as in type-II pneumocytes as of in by the of and to the and to in the to protease as pneumocytes by and to of by as by the type-II pneumocytes in of and of the by the in of a SP-B to an the as and a as a and of the to and and the the and the and a the of the expressed protein. protein of and a of of as as the and in to an of to the to a of to the and the by in and by and in in the of the of the to a and the protein and in in the the by napsin A by a of as of and as and a SP-B by and and by of and the of and in a of and in an To to the the in in the the to the of the as in and and as in in the by of a of and in the the of to the of by a in and in to in to a of and to and to the To and the in and in the to the in and by a in and the a of and SP-B and napsin as the napsin A and the SP-B in by a and in we and A as and in a of by a by of the of the and and the and of of to the in and to and the to in the of the Napsin of napsin A in the napsin A by the of the a and in protease and of of and the by the of of a of an in the and of Napsin and of napsin A as an napsin A Napsin A the the propeptide and napsin A and in of Napsin A napsin A in and napsin A as well as in the of napsin A and as well as in the of and the by as in the of in and of the and type-II pneumocytes and by and to to the of the the and of the to the and the of Napsin A of napsin A of napsin and of in a a in of the the by and of by Napsin A of SP-B napsin A as by in and SP-B the the a by and of and the in a and of and the by of a of and by and in a the in and a in of and in a a in of the the the we and the the of as as the by by and by and in of the and a by of the the to and as in type-II pneumocytes as of in by the of and to the and to in the to protease as pneumocytes by and to of by as by the type-II pneumocytes in of and of the by the in of a SP-B to an the as and a as a and of the to and and the the and the and a the of the expressed protein. protein of and a of of as as the and in to an of to the to a of to the and the by in and by and in in the of the of the to a and the protein and in in the the by napsin A by a of as of and as and a SP-B by and and by of and the of and in a of and in an To to the the in in the the to the of the as in and and as in in the by of a of and in the the of to the of by a in and in to in to a of and to and to the To and the in and in the to the in and by a in and the a of and SP-B and napsin as the napsin A and the SP-B in by a and in we and A as and in a of by a by of the of the and and the and of of to the in and to and the to in the of the Napsin of napsin A in the napsin A by the of the a and in protease and of of and the by the of of a of an in the and of Napsin and of napsin A as an napsin A Napsin A the the propeptide and napsin A and in of Napsin A napsin A in and napsin A as well as in the of napsin A and as well as in the of and the by as in the of in and of the and type-II pneumocytes and by and to to the of the the and of the to the and the of Napsin A of napsin A of napsin and of in a a in of the the by and of by Napsin A of SP-B napsin A as by in and SP-B the the a by and of and the in a and of and the by of a of and by and in a the in and a in of and in a a in of the the of in napsin in type-II pneumocytes. an the as well as a in type-II napsin A in the Golgi and in the napsin A in the and in of the a and the of the and is a the processing in we A and napsin A and napsin A and colocalized in a a and napsin A and SP-B colocalized in multivesicular, composite, and and Napsin A in and napsin A is synthesized as an and napsin A the and the we napsin A in and in type-II pneumocytes. A in the the of the to napsin A and of the by of the aspartic protease of by Napsin napsin A to in of napsin and by the SP-B and a and the processing of by the of a and of in and in processing by napsin A and and processing and and processing by the SP-B and and the the processing of by napsin A by the of and To the of napsin A and the processing in we in the of the protease the aspartic protease the processing by type-II pneumocytes of and an SP-B and by to and the to and and of Napsin A we the we napsin A and the of the to the in the and the of the by of the in of by napsin to a the and a the napsin the and by as and of the processing the of the by of the of the the and the of and A which by napsin to of by the of napsin A the we processing by the and the as the by napsin A To of in by is by an aspartic protease we an of an of aspartic the processing of by to the of by napsin A to the of the protein a to the napsin A we a of the and of by napsin A and by and to of in To the an and the by in the of napsin A and the of the processing by the of the of the protein by napsin A of by napsin A processing processing processing in a in processing in SP-B precursors in we type-II pneumocytes. type-II and SP-B precursors of and and by to and the to and and of the processing well to of the by napsin A we a protease in the of SP-B precursors we to an of processing by napsin A in type-II pneumocytes we type-II pneumocytes of and SP-B precursors by and and and of the of SP-B well to of the by napsin A of processing in type-II pneumocytes of of in as well as and precursors of SP-B in type-II pneumocytes and and which in and and of in napsin in type-II pneumocytes. an the as well as a in type-II napsin A in the Golgi and in the napsin A in the and in of the a and the of the and is a the processing in we A and napsin A and napsin A and colocalized in a a and napsin A and SP-B colocalized in multivesicular, composite, and and Napsin A in and napsin A is synthesized as an and napsin A the and the we napsin A in and in type-II pneumocytes. A in the the of the to napsin A and of the by of the aspartic protease of by Napsin napsin A to in of napsin and by the SP-B and a and the processing of by the of a and of Napsin A we the we napsin A and the of the to the in the and the of the by of the in of by the of napsin A the we processing by the and the as the by napsin A To of in by is by an aspartic protease we an of an of aspartic the processing of by to the of by napsin A to the of the protein a to the napsin A we a of the and of by napsin A and by and to of in To the an and the by in the of napsin A and the of the processing by the of the of the protein by napsin A in processing in SP-B precursors in we type-II pneumocytes. type-II and SP-B precursors of and and by to and the to and and of the processing well to of the by napsin A we a protease in the of SP-B precursors we to an of processing by napsin A in type-II pneumocytes we type-II pneumocytes of and SP-B precursors by and and and of the of SP-B well to of the by napsin A a role in SP-B is synthesized as a processing is a A of SP-B precursors of SP-B in of and the of precursors of SP-B in and pulmonary a pulmonary to a of processing of A deficiency of the in the processing a a protease to the processing of in type-II pneumocytes by by and in we the aspartic protease napsin which in type-II pneumocytes of the the aspartic protease napsin A is a and SP-B a we napsin precursors of and SP-B in the by the propeptide of precursors of SP-B in the and Golgi in a in we SP-B in multivesicular, composite, and type-II pneumocytes in in Golgi Napsin A to colocalized precursors of SP-B SP-B in Golgi and SP-B and napsin A in which the the of and in and SP-B is the Golgi the and to the and the processing of in the Golgi and napsin A and precursors of SP-B as well as SP-B colocalized in type-II pneumocytes napsin A in the processing of we napsin A is active in type-II pneumocytes in the of napsin A well the in and the processing of by napsin we as well as napsin and in processing the of the protein is to the of the protein and a napsin A processing to processing by an aspartic protease in to we the processing in type-II pneumocytes. the and the of SP-B the propeptide in we a of the of SP-B well to of the in of an processing in type-II which well to the in the processing is the of SP-B in type-II pneumocytes we the napsin A the protein. of the processing the SP-B and of the as well as the of the of the propeptide to the processing the and in the propeptide in an and in the processing by napsin A and in a in the propeptide and the processing of processing is by an by a a and a processing of processing in which in pneumocytes the processing a the of SP-B and the the processing to the in of SP-B in the napsin A and the processing and a processing in type-II pneumocytes of an processing of to an of the role of napsin A in the processing of in to napsin in of of of the in the processing of and in an of and results napsin A is in the processing of in type-II pneumocytes in the of the of napsin A in the and processing of we a of napsin A and precursors of SP-B as well as SP-B in the in type-II pneumocytes. and type-II pneumocytes napsin A napsin A and processing of of processing of in the and propeptide as well as in the of by napsin A in the of the aspartic protease processing of in in type-II pneumocytes the processing of in by napsin A and in type-II pneumocytes of protease processing of is by by a napsin A to SP-B in in the of the and of protease is a the of the and of the processing to napsin A the the pulmonary as is in processing of SP-B a role in SP-B is synthesized as a processing is a A of SP-B precursors of SP-B in of and the of precursors of SP-B in and pulmonary a pulmonary to a of processing of A deficiency of the in the processing a a protease to the processing of in type-II pneumocytes by by and in we the aspartic protease napsin which in type-II pneumocytes of the the aspartic protease napsin A is a and SP-B a we napsin precursors of and SP-B in the by the propeptide of precursors of SP-B in the and Golgi in a in we SP-B in multivesicular, composite, and type-II pneumocytes in in Golgi Napsin A to colocalized precursors of SP-B SP-B in Golgi and SP-B and napsin A in which the the of and in and SP-B is the Golgi the and to the and the processing of in the Golgi and napsin A and precursors of SP-B as well as SP-B colocalized in type-II pneumocytes napsin A in the processing of we napsin A is active in type-II pneumocytes in the of napsin A well the in and To the processing of by napsin we as well as napsin and in processing the of the protein is to the of the protein and a napsin A processing to processing by an aspartic protease in to we the processing in type-II pneumocytes. the and the of SP-B the propeptide in we a of the of SP-B well to of the in of an processing in type-II which well to the in the processing is the of SP-B in type-II pneumocytes we the napsin A the protein. of the processing the SP-B and of the as well as the of the of the propeptide to the processing the and in the propeptide in an and in the processing by napsin A and in a in the propeptide and the processing of processing is by an by a a and a processing of processing in which in pneumocytes the processing a the of SP-B and the the processing to the in of SP-B in the napsin A and the processing and a processing in type-II pneumocytes of an processing of to an of the role of napsin A in the processing of in to napsin in of of of the in the processing of and in an of and results napsin A is in the processing of in type-II pneumocytes in the of the of napsin A in the and processing of we a of napsin A and precursors of SP-B as well as SP-B in the in type-II pneumocytes. and type-II pneumocytes napsin A napsin A and processing of of processing of in the and propeptide as well as in the of by napsin A in the of the aspartic protease processing of in in type-II pneumocytes the processing of in by napsin A and in type-II pneumocytes of protease processing of is by by a napsin A to SP-B in in the of the and of protease is a the of the and of the processing to napsin A the the pulmonary as is in processing of and and and