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Centriolar Association of ALMS1 and Likely Centrosomal Functions of the ALMS Motif–containing Proteins C10orf90 and KIAA1731

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...

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Autores principales: Knorz, Victoria J., Spalluto, Cosma, Lessard, Mark, Purvis, Tracey L., Adigun, Fiona F., Collin, Gayle B., Hanley, Neil A., Wilson, David I., Hearn, Thomas
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2965680/
https://www.ncbi.nlm.nih.gov/pubmed/20844083
http://dx.doi.org/10.1091/mbc.E10-03-0246
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author Knorz, Victoria J.
Spalluto, Cosma
Lessard, Mark
Purvis, Tracey L.
Adigun, Fiona F.
Collin, Gayle B.
Hanley, Neil A.
Wilson, David I.
Hearn, Thomas
author_facet Knorz, Victoria J.
Spalluto, Cosma
Lessard, Mark
Purvis, Tracey L.
Adigun, Fiona F.
Collin, Gayle B.
Hanley, Neil A.
Wilson, David I.
Hearn, Thomas
author_sort Knorz, Victoria J.
collection PubMed
description 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.
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spelling pubmed-29656802011-01-16 Centriolar Association of ALMS1 and Likely Centrosomal Functions of the ALMS Motif–containing Proteins C10orf90 and KIAA1731 Knorz, Victoria J. Spalluto, Cosma Lessard, Mark Purvis, Tracey L. Adigun, Fiona F. Collin, Gayle B. Hanley, Neil A. Wilson, David I. Hearn, Thomas Mol Biol Cell Articles 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. The American Society for Cell Biology 2010-11-01 /pmc/articles/PMC2965680/ /pubmed/20844083 http://dx.doi.org/10.1091/mbc.E10-03-0246 Text en © 2010 by The American Society for Cell Biology This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
spellingShingle Articles
Knorz, Victoria J.
Spalluto, Cosma
Lessard, Mark
Purvis, Tracey L.
Adigun, Fiona F.
Collin, Gayle B.
Hanley, Neil A.
Wilson, David I.
Hearn, Thomas
Centriolar Association of ALMS1 and Likely Centrosomal Functions of the ALMS Motif–containing Proteins C10orf90 and KIAA1731
title Centriolar Association of ALMS1 and Likely Centrosomal Functions of the ALMS Motif–containing Proteins C10orf90 and KIAA1731
title_full Centriolar Association of ALMS1 and Likely Centrosomal Functions of the ALMS Motif–containing Proteins C10orf90 and KIAA1731
title_fullStr Centriolar Association of ALMS1 and Likely Centrosomal Functions of the ALMS Motif–containing Proteins C10orf90 and KIAA1731
title_full_unstemmed Centriolar Association of ALMS1 and Likely Centrosomal Functions of the ALMS Motif–containing Proteins C10orf90 and KIAA1731
title_short Centriolar Association of ALMS1 and Likely Centrosomal Functions of the ALMS Motif–containing Proteins C10orf90 and KIAA1731
title_sort centriolar association of alms1 and likely centrosomal functions of the alms motif–containing proteins c10orf90 and kiaa1731
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2965680/
https://www.ncbi.nlm.nih.gov/pubmed/20844083
http://dx.doi.org/10.1091/mbc.E10-03-0246
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