NudC-like protein 2 regulates the LIS1/dynein pathway by stabilizing LIS1 with Hsp90.
The type I lissencephaly gene product LIS1, a key regulator of cytoplasmic dynein, is critical for cell proliferation, survival, and neuronal migration. However, little is known about the regulation of LIS1. Here, we identify a previously uncharacterized mammalian homolog of Aspergillus NudC, NudCL2 (NudC-like protein 2), as a regulator of LIS1. NudCL2 is localized to the centrosome in interphase, and spindle poles and kinetochores during mitosis, a pattern similar to the localization of LIS1 and cytoplasmic dynein. Depletion of NudCL2 destabilized LIS1 and led to phenotypes resembling those of either dynein or LIS1 deficiency. NudCL2 complexed with and enhanced the interaction between LIS1 and Hsp90. Either disruption of the LIS1-Hsp90 interaction with the C terminus of NudCL2 or inhibition of Hsp90 chaperone function by geldanamycin decreased LIS1 stability. Thus, our results suggest that NudCL2 regulates the LIS1/dynein pathway by stabilizing LIS1 with Hsp90 chaperone. This represents a hitherto undescribed mechanism of the LIS1/dynein regulation in mammalian cells.
Yang
Yuehong
Y
Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
Yan
Xiaoyi
X
Cai
Yuqi
Y
Lu
Yiqing
Y
Si
Jianmin
J
Zhou
Tianhua
T
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D015536:Down-Regulation; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D055550:Protein Stability
D002352:Carrier Proteins; D018841:HSP90 Heat-Shock Proteins; D008869:Microtubule-Associated Proteins; C548331:NUDCD2 protein, human; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human