Centriolar Association of ALMS1 and Likely Centrosomal Functions of the ALMS Motif–containing Proteins C10orf90 and KIAA1731
Open Access
- 1 November 2010
- journal article
- research article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 21 (21), 3617-3629
- https://doi.org/10.1091/mbc.e10-03-0246
Abstract
Mutations in the human gene ALMS1 cause Alström syndrome, a rare progressive condition characterized by neurosensory degeneration and metabolic defects. ALMS1 protein localizes to the centrosome and has been implicated in the assembly and/or maintenance of primary cilia; however its precise function, distribution within the centrosome, and mechanism of centrosomal recruitment are unknown. The C-terminus of ALMS1 contains a region with similarity to the uncharacterized human protein C10orf90, termed the ALMS motif. Here, we show that a third human protein, the candidate centrosomal protein KIAA1731, contains an ALMS motif and that exogenously expressed KIAA1731 and C10orf90 localize to the centrosome. However, based on deletion analysis of ALMS1, the ALMS motif appears unlikely to be critical for centrosomal targeting. RNAi analyses suggest that C10orf90 and KIAA1731 have roles in primary cilium assembly and centriole formation/stability, respectively. We also show that ALMS1 localizes specifically to the proximal ends of centrioles and basal bodies, where it colocalizes with the centrosome cohesion protein C-Nap1. RNAi analysis reveals markedly diminished centrosomal levels of C-Nap1 and compromised cohesion of parental centrioles in ALMS1-depleted cells. In summary, these data suggest centrosomal functions for C10orf90 and KIAA1731 and new centriole-related functions for ALMS1.Keywords
This publication has 70 references indexed in Scilit:
- Drosophila Ana2 is a conserved centriole duplication factorThe Journal of cell biology, 2010
- Dimerization of CPAP Orchestrates Centrosome Cohesion PlasticityPublished by Elsevier BV ,2010
- Ana3 is a conserved protein required for the structural integrity of centrioles and basal bodiesThe Journal of cell biology, 2009
- Overly Long Centrioles and Defective Cell Division upon Excess of the SAS-4-Related Protein CPAPCurrent Biology, 2009
- CEP290 interacts with the centriolar satellite component PCM-1 and is required for Rab8 localization to the primary ciliumHuman Molecular Genetics, 2008
- The cell biological basis of ciliary diseaseThe Journal of cell biology, 2008
- β-Catenin is a Nek2 substrate involved in centrosome separationGenes & Development, 2007
- Cep164, a novel centriole appendage protein required for primary cilium formationThe Journal of cell biology, 2007
- Plk4-Induced Centriole Biogenesis in Human CellsDevelopmental Cell, 2007
- Proteomic characterization of the human centrosome by protein correlation profilingNature, 2003