A fraction of Crm1 locates at centrosomes by its CRIME domain and regulates the centrosomal localization of pericentrin.
Crm1 plays a role in exporting proteins containing nuclear export signals (NESs) from the nucleus to the cytoplasm. Some proteins that are capable of interacting with Ran/Crm1 were reported to be localized at centrosomes and to function as centrosome checkpoints. But it remains unclear how Crm1 locates at centrosomes. In this study, we found that a fraction of Crm1 is located at centrosomes through its N-terminal CRM1, importin beta etc. (CRIME) domain, which is responsible for interacting with RanGTP, suggesting that Crm1 might target to centrosomes through binding centrosomal RanGTP. Moreover, overexpression of the CRIME domain, which is free of NES binding domain, resulted in the dissociation of pericentrin and gamma-tubulin complex from centrosomes and the disruption of microtubule nucleation. Deficiency of Crm1 provoked by RNAi also decreased the spindle poles localization of pericentrin and gamma-tubulin complex, coupled with mitotic defects. Since pericentrin was sensitive to Crm1 specific inhibitor leptomycin B, we propose that the centrosomal Crm1 might interact with pericentrin and regulate the localization and function of pericentrin at centrosomes.
Liu
Qinying
Q
The MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking University, Beijing 100871, China.
Jiang
Qing
Q
Zhang
Chuanmao
C
D000818:Animals; D000941:Antigens / Q000235:genetics / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000235:genetics; D041681:NIH 3T3 Cells; D017434:Protein Structure, Tertiary / Q000235:genetics; D034622:RNA Interference; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D014981:Xenopus; D000097606:Exportin 1 Protein
D000941:Antigens; D028884:Karyopherins; D018160:Receptors, Cytoplasmic and Nuclear; D014404:Tubulin; D000097606:Exportin 1 Protein; C086178:pericentrin