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Constitutive Cleavage of the Single-Pass Transmembrane Protein Alcadeinα Prevents Aberrant Peripheral Retention of Kinesin-1

Various membrane proteins are shed by proteinases, constitutively and/or when stimulated by external signals. While the physiological significance of external signal-induced cleavages has been intensely investigated, relatively little is known about the function of constitutive cleavages. Alcadeinα...

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Autores principales: Maruta, Chiaki, Saito, Yuhki, Hata, Saori, Gotoh, Naoya, Suzuki, Toshiharu, Yamamoto, Tohru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3414480/
https://www.ncbi.nlm.nih.gov/pubmed/22905201
http://dx.doi.org/10.1371/journal.pone.0043058
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author Maruta, Chiaki
Saito, Yuhki
Hata, Saori
Gotoh, Naoya
Suzuki, Toshiharu
Yamamoto, Tohru
author_facet Maruta, Chiaki
Saito, Yuhki
Hata, Saori
Gotoh, Naoya
Suzuki, Toshiharu
Yamamoto, Tohru
author_sort Maruta, Chiaki
collection PubMed
description Various membrane proteins are shed by proteinases, constitutively and/or when stimulated by external signals. While the physiological significance of external signal-induced cleavages has been intensely investigated, relatively little is known about the function of constitutive cleavages. Alcadeinα (Alcα; also called Calsyntenin-1) is an evolutionarily conserved type I single-pass transmembrane protein that binds to kinesin-1 light chain (KLC) to activate kinesin-1's transport of Alcα-containing vesicles. We found that Alcα was constitutively and efficiently cleaved to liberate its ectodomain into the extracellular space, and that full-length Alcα protein was rarely detected on the cell surface. The secretion efficiency of the ectodomain was unaltered by a mutation that both abolished Alcα's KLC-binding activity and attenuated its peripheral transport, suggesting that Alcα's cleavage occurred, at least partly, en route to the cell surface. We further demonstrated that uncleavable mutant Alcα proteins readily accumulated on the cell surface and induced aberrant peripheral recruitment of KLC1 and kinesin heavy chain. Our observations suggest that Alcα is efficiently processed in part to minimize the inappropriate peripheral retention of kinesin-1. This role might exemplify the functional relevance of the constitutive cleavage of single-pass transmembrane proteins.
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spelling pubmed-34144802012-08-19 Constitutive Cleavage of the Single-Pass Transmembrane Protein Alcadeinα Prevents Aberrant Peripheral Retention of Kinesin-1 Maruta, Chiaki Saito, Yuhki Hata, Saori Gotoh, Naoya Suzuki, Toshiharu Yamamoto, Tohru PLoS One Research Article Various membrane proteins are shed by proteinases, constitutively and/or when stimulated by external signals. While the physiological significance of external signal-induced cleavages has been intensely investigated, relatively little is known about the function of constitutive cleavages. Alcadeinα (Alcα; also called Calsyntenin-1) is an evolutionarily conserved type I single-pass transmembrane protein that binds to kinesin-1 light chain (KLC) to activate kinesin-1's transport of Alcα-containing vesicles. We found that Alcα was constitutively and efficiently cleaved to liberate its ectodomain into the extracellular space, and that full-length Alcα protein was rarely detected on the cell surface. The secretion efficiency of the ectodomain was unaltered by a mutation that both abolished Alcα's KLC-binding activity and attenuated its peripheral transport, suggesting that Alcα's cleavage occurred, at least partly, en route to the cell surface. We further demonstrated that uncleavable mutant Alcα proteins readily accumulated on the cell surface and induced aberrant peripheral recruitment of KLC1 and kinesin heavy chain. Our observations suggest that Alcα is efficiently processed in part to minimize the inappropriate peripheral retention of kinesin-1. This role might exemplify the functional relevance of the constitutive cleavage of single-pass transmembrane proteins. Public Library of Science 2012-08-08 /pmc/articles/PMC3414480/ /pubmed/22905201 http://dx.doi.org/10.1371/journal.pone.0043058 Text en © 2012 Maruta et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Maruta, Chiaki
Saito, Yuhki
Hata, Saori
Gotoh, Naoya
Suzuki, Toshiharu
Yamamoto, Tohru
Constitutive Cleavage of the Single-Pass Transmembrane Protein Alcadeinα Prevents Aberrant Peripheral Retention of Kinesin-1
title Constitutive Cleavage of the Single-Pass Transmembrane Protein Alcadeinα Prevents Aberrant Peripheral Retention of Kinesin-1
title_full Constitutive Cleavage of the Single-Pass Transmembrane Protein Alcadeinα Prevents Aberrant Peripheral Retention of Kinesin-1
title_fullStr Constitutive Cleavage of the Single-Pass Transmembrane Protein Alcadeinα Prevents Aberrant Peripheral Retention of Kinesin-1
title_full_unstemmed Constitutive Cleavage of the Single-Pass Transmembrane Protein Alcadeinα Prevents Aberrant Peripheral Retention of Kinesin-1
title_short Constitutive Cleavage of the Single-Pass Transmembrane Protein Alcadeinα Prevents Aberrant Peripheral Retention of Kinesin-1
title_sort constitutive cleavage of the single-pass transmembrane protein alcadeinα prevents aberrant peripheral retention of kinesin-1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3414480/
https://www.ncbi.nlm.nih.gov/pubmed/22905201
http://dx.doi.org/10.1371/journal.pone.0043058
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