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MCRS1 associates with cytoplasmic dynein and mediates pericentrosomal material recruitment

 Si-Hyung Lee  ;  Mi-Sun Lee  ;  Tae-Ik Choi  ;  Hyowon Hong  ;  Jun-Young Seo  ;  Cheol-Hee Kim  ;  Joon Kim 
 SCIENTIFIC REPORTS, Vol.6 : 27284, 2016 
Journal Title
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Animals ; Centrosome/metabolism* ; Cilia/metabolism ; Cytoplasmic Dyneins/metabolism* ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; Microtubule-Associated Proteins/metabolism ; Nuclear Proteins/genetics* ; Nuclear Proteins/metabolism* ; Protein Transport ; Protein-Serine-Threonine Kinases/metabolism ; RNA-Binding Proteins/genetics* ; RNA-Binding Proteins/metabolism* ; Zebrafish
MCRS1 is involved in multiple cellular activities, including mitotic spindle assembly, mTOR signaling and tumorigenesis. Although MCRS1 has been reported to bind to the dynein regulator NDE1, a functional interaction between MCRS1 and cytoplasmic dynein remains unaddressed. Here, we demonstrate that MCRS1 is required for dynein-dependent cargo transport to the centrosome and also plays a role in primary cilium formation. MCRS1 localized to centriolar satellites. Knockdown of MCRS1 resulted in a dispersion of centriolar satellites whose establishment depends on cytoplasmic dynein. By contrast, NDE1 was not necessary for the proper distribution of centriolar satellites, indicating a functional distinction between MCRS1 and NDE1. Unlike NDE1, MCRS1 played a positive role for the initiation of ciliogenesis, possibly through its interaction with TTBK2. Zebrafish with homozygous mcrs1 mutants exhibited a reduction in the size of the brain and the eye due to excessive apoptosis. In addition, mcrs1 mutants failed to develop distinct layers in the retina, and showed a defect in melatonin-induced aggregation of melanosomes in melanophores. These phenotypes are reminiscent of zebrafish dynein mutants. Reduced ciliogenesis was also apparent in the olfactory placode of mcrs1 mutants. Collectively, our findings identify MCRS1 as a dynein-interacting protein critical for centriolar satellite formation and ciliogenesis.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
Seo, Jun Young(서준영) ORCID logo https://orcid.org/0000-0003-4004-2013
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