Clusterin interacts with SCLIP (SCG10-like protein) and promotes neurite outgrowth of PC12 cells.
Clusterin has been known as a chaperone-like molecule capable of interacting with various proteins. In this study, we show that clusterin interacts with the microtubule-destabilizing stathmin family protein SCLIP by GST pull-down and co-immunoprecipitation assays. Interestingly, SCLIP interacts with 80 kDa mature form of clusterin in the cytosolic fraction of PC12 cells permeabilized by low concentration of a weak nonionic detergent digitonin, but not with intracellular variants of clusterin known as binding isoforms of Ku70 or TGF-beta receptors. Both clusterin and SCLIP are co-localized at the perinuclear region and growth cone of PC12 cells. In addition, we show that the minimal domains for the interaction are mapped to the C-terminal valine-rich region (367-447) of clusterin and the N-terminal palmitoylation and membrane attachment site (1-34) of SCLIP. Finally, we demonstrate that ectopic expression of clusterin in PC12 cells elongates neurite-formation triggered by NGF and induces spontaneous neurite outgrowth even in the absence of NGF. Taken together, these results suggest that the clusterin interacts with SCLIP and the interaction may act as an important modulator during neuronal differentiation.
Kang
Sang-Wook
SW
Department of Pharmacology and BK21 Program for Medical Sciences, College of Medicine, Korea University, 126-1 Anam-dong 5-Ga, Sungbuk-Gu, Seoul 136-705, Korea.
Shin
Yong-Jae
YJ
Shim
Young-Jun
YJ
Jeong
Seong-Yun
SY
Park
In-Sun
IS
Min
Bon-Hong
BH
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D003593:Cytoplasm / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism*; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology; D016716:PC12 Cells; D017434:Protein Structure, Tertiary; D051381:Rats; D050053:TRPM Cation Channels
D007473:Ion Channels; D008565:Membrane Proteins; D009414:Nerve Growth Factors; C491792:Stmn3 protein, rat; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human