title: Centriolar association of ALMS1 and likely centrosomal functions of the ALMS motif-containing proteins C10orf90 and KIAA1731.
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.
authors.affiliation: Centre for Human Development, Stem Cells and Regeneration, Human Genetics Division, University of Southampton, Southampton, United Kingdom.
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Knorz
authors.forename: Cosma
authors.initials: C
authors.lastname: Spalluto
authors.forename: Mark
authors.initials: M
authors.lastname: Lessard
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Purvis
authors.forename: Fiona F
authors.initials: FF
authors.lastname: Adigun
authors.forename: Gayle B
authors.initials: GB
authors.lastname: Collin
authors.forename: Neil A
authors.initials: NA
authors.lastname: Hanley
authors.forename: David I
authors.initials: DI
authors.lastname: Wilson
authors.forename: Thomas
authors.initials: T
authors.lastname: Hearn
mesh_terms: D056769:Alstrom Syndrome / Q000235:genetics; D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins; D002460:Cell Line; D002502:Centrioles / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017124:Conserved Sequence; D003598:Cytoskeletal Proteins; D017353:Gene Deletion; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: C490729:ALMS1 protein, human; C556020:C10orf90 protein, human; C556019:CEP295 protein, human; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D003598:Cytoskeletal Proteins; D008869:Microtubule-Associated Proteins; D011506:Proteins; D034741:RNA, Small Interfering