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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Li, Lian Lee, Samuel M. Chin, Lih-shen |
| Description | Author Affiliation: Lee SM ( Department of Pharmacology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA.) |
| Abstract | Mutations in small integral membrane protein of lysosome/late endosome (SIMPLE) cause autosomal dominant, Charcot-Marie-Tooth disease (CMT) type 1C. The cellular function of SIMPLE is unknown and the pathogenic mechanism of SIMPLE mutations remains elusive. Here, we report that SIMPLE interacted and colocalized with endosomal sorting complex required for transport (ESCRT) components STAM1, Hrs, and TSG101 on early endosomes and functioned with the ESCRT machinery in the control of endosome-to-lysosome trafficking. Our analyses revealed that SIMPLE was required for efficient recruitment of ESCRT components to endosomal membranes and for regulating endosomal trafficking and signaling attenuation of ErbB receptors. We found that the ability of SIMPLE to regulate ErbB trafficking and signaling was impaired by CMT-linked SIMPLE mutations via a loss-of-function, dominant-negative mechanism, resulting in prolonged activation of ERK1/2 signaling. Our findings indicate a function of SIMPLE as a regulator of endosomal trafficking and provide evidence linking dysregulated endosomal trafficking to CMT pathogenesis. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 5 |
| Volume Number | 199 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 2012-11-26 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Charcot-Marie-Tooth Disease Metabolism Endosomal Sorting Complexes Required For Transport Endosomes Nuclear Proteins Transcription Factors Animals Biological Transport Extracellular Signal-Regulated MAP Kinases HeLa Cells MAP Kinase Signaling System Mice Schwann Cells Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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