MCRS1 associates with cytoplasmic dynein and mediates pericentrosomal material recruitment.
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.
Graduate School of Medical Science and Engineering, KAIST, Daejeon 34141, Korea.
Si-Hyung
SH
Lee
Department of Biology, Chungnam National University, Daejeon 34134, Korea.
Mi-Sun
MS
Lee
Department of Biology, Chungnam National University, Daejeon 34134, Korea.
Tae-Ik
TI
Choi
Graduate School of Medical Science and Engineering, KAIST, Daejeon 34141, Korea.
Hyowon
H
Hong
Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea.
Jun-Young
JY
Seo
Department of Biology, Chungnam National University, Daejeon 34134, Korea.
Cheol-Hee
CH
Kim
Graduate School of Medical Science and Engineering, KAIST, Daejeon 34141, Korea.
Joon
J
Kim
D000818:Animals; D018385:Centrosome / Q000378:metabolism*; D002923:Cilia / Q000378:metabolism; D056445:Cytoplasmic Dyneins / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D015027:Zebrafish
C113292:MCRS1 protein, human; D008869:Microtubule-Associated Proteins; C525094:Nde1 protein, human; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C095903:tau-tubulin kinase; D017346:Protein Serine-Threonine Kinases; D056445:Cytoplasmic Dyneins