Phosphoinositide regulation of integrin trafficking required for muscle attachment and maintenance.
Muscles must maintain cell compartmentalization when remodeled during development and use. How spatially restricted adhesions are regulated with muscle remodeling is largely unexplored. We show that the myotubularin (mtm) phosphoinositide phosphatase is required for integrin-mediated myofiber attach...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-02-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC3037412?pdf=render |
| _version_ | 1818838600168505344 |
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| author | Inês Ribeiro Lin Yuan Guy Tanentzapf James J Dowling Amy Kiger |
| author_facet | Inês Ribeiro Lin Yuan Guy Tanentzapf James J Dowling Amy Kiger |
| author_sort | Inês Ribeiro |
| collection | DOAJ |
| description | Muscles must maintain cell compartmentalization when remodeled during development and use. How spatially restricted adhesions are regulated with muscle remodeling is largely unexplored. We show that the myotubularin (mtm) phosphoinositide phosphatase is required for integrin-mediated myofiber attachments in Drosophila melanogaster, and that mtm-depleted myofibers exhibit hallmarks of human XLMTM myopathy. Depletion of mtm leads to increased integrin turnover at the sarcolemma and an accumulation of integrin with PI(3)P on endosomal-related membrane inclusions, indicating a role for Mtm phosphatase activity in endocytic trafficking. The depletion of Class II, but not Class III, PI3-kinase rescued mtm-dependent defects, identifying an important pathway that regulates integrin recycling. Importantly, similar integrin localization defects found in human XLMTM myofibers signify conserved MTM1 function in muscle membrane trafficking. Our results indicate that regulation of distinct phosphoinositide pools plays a central role in maintaining cell compartmentalization and attachments during muscle remodeling, and they suggest involvement of Class II PI3-kinase in MTM-related disease. |
| first_indexed | 2024-12-19T03:40:58Z |
| format | Article |
| id | doaj.art-a1b6b81f769449488f157582810495cd |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-19T03:40:58Z |
| publishDate | 2011-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-a1b6b81f769449488f157582810495cd2022-12-21T20:37:15ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042011-02-0172e100129510.1371/journal.pgen.1001295Phosphoinositide regulation of integrin trafficking required for muscle attachment and maintenance.Inês RibeiroLin YuanGuy TanentzapfJames J DowlingAmy KigerMuscles must maintain cell compartmentalization when remodeled during development and use. How spatially restricted adhesions are regulated with muscle remodeling is largely unexplored. We show that the myotubularin (mtm) phosphoinositide phosphatase is required for integrin-mediated myofiber attachments in Drosophila melanogaster, and that mtm-depleted myofibers exhibit hallmarks of human XLMTM myopathy. Depletion of mtm leads to increased integrin turnover at the sarcolemma and an accumulation of integrin with PI(3)P on endosomal-related membrane inclusions, indicating a role for Mtm phosphatase activity in endocytic trafficking. The depletion of Class II, but not Class III, PI3-kinase rescued mtm-dependent defects, identifying an important pathway that regulates integrin recycling. Importantly, similar integrin localization defects found in human XLMTM myofibers signify conserved MTM1 function in muscle membrane trafficking. Our results indicate that regulation of distinct phosphoinositide pools plays a central role in maintaining cell compartmentalization and attachments during muscle remodeling, and they suggest involvement of Class II PI3-kinase in MTM-related disease.http://europepmc.org/articles/PMC3037412?pdf=render |
| spellingShingle | Inês Ribeiro Lin Yuan Guy Tanentzapf James J Dowling Amy Kiger Phosphoinositide regulation of integrin trafficking required for muscle attachment and maintenance. PLoS Genetics |
| title | Phosphoinositide regulation of integrin trafficking required for muscle attachment and maintenance. |
| title_full | Phosphoinositide regulation of integrin trafficking required for muscle attachment and maintenance. |
| title_fullStr | Phosphoinositide regulation of integrin trafficking required for muscle attachment and maintenance. |
| title_full_unstemmed | Phosphoinositide regulation of integrin trafficking required for muscle attachment and maintenance. |
| title_short | Phosphoinositide regulation of integrin trafficking required for muscle attachment and maintenance. |
| title_sort | phosphoinositide regulation of integrin trafficking required for muscle attachment and maintenance |
| url | http://europepmc.org/articles/PMC3037412?pdf=render |
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