| First Author | Collin GB | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 5 | Pages | e37925 |
| PubMed ID | 22693585 | Mgi Jnum | J:187422 |
| Mgi Id | MGI:5436381 | Doi | 10.1371/journal.pone.0037925 |
| Citation | Collin GB, et al. (2012) The Alstrom syndrome protein, ALMS1, interacts with alpha-actinin and components of the endosome recycling pathway. PLoS One 7(5):e37925 |
| abstractText | Alstrom syndrome (ALMS) is a progressive multi-systemic disorder characterized by cone-rod dystrophy, sensorineural hearing loss, childhood obesity, insulin resistance and cardiac, renal, and hepatic dysfunction. The gene responsible for Alstrom syndrome, ALMS1, is ubiquitously expressed and has multiple splice variants. The protein encoded by this gene has been implicated in ciliary function, cell cycle control, and intracellular transport. To gain better insight into the pathways through which ALMS1 functions, we carried out a yeast two hybrid (Y2H) screen in several mouse tissue libraries to identify ALMS1 interacting partners. The majority of proteins found to interact with the murine carboxy-terminal end (19/32) of ALMS1 were alpha-actinin isoforms. Interestingly, several of the identified ALMS1 interacting partners (alpha-actinin 1, alpha-actinin 4, myosin Vb, rad50 interacting 1 and huntingtin associated protein1A) have been previously associated with endosome recycling and/or centrosome function. We examined dermal fibroblasts from human subjects bearing a disruption in ALMS1 for defects in the endocytic pathway. Fibroblasts from these patients had a lower uptake of transferrin and reduced clearance of transferrin compared to controls. Antibodies directed against ALMS1 N- and C-terminal epitopes label centrosomes and endosomal structures at the cleavage furrow of dividing MDCK cells, respectively, suggesting isoform-specific cellular functions. Our results suggest a role for ALMS1 variants in the recycling endosome pathway and give us new insights into the pathogenesis of a subset of clinical phenotypes associated with ALMS. |
