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Conformational changes in CLIP-170 regulate its binding to microtubules and dynactin localization
Authors:Lansbergen Gideon  Komarova Yulia  Modesti Mauro  Wyman Claire  Hoogenraad Casper C  Goodson Holly V  Lemaitre Régis P  Drechsel David N  van Munster Erik  Gadella Theodorus W J  Grosveld Frank  Galjart Niels  Borisy Gary G  Akhmanova Anna
Institution:MGC Dept. of Cell Biology and of Genetics, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, Netherlands.
Abstract:Cytoplasmic linker protein (CLIP)-170, CLIP-115, and the dynactin subunit p150(Glued) are structurally related proteins, which associate specifically with the ends of growing microtubules (MTs). Here, we show that down-regulation of CLIP-170 by RNA interference results in a strongly reduced accumulation of dynactin at the MT tips. The NH(2) terminus of p150(Glued) binds directly to the COOH terminus of CLIP-170 through its second metal-binding motif. p150(Glued) and LIS1, a dynein-associating protein, compete for the interaction with the CLIP-170 COOH terminus, suggesting that LIS1 can act to release dynactin from the MT tips. We also show that the NH(2)-terminal part of CLIP-170 itself associates with the CLIP-170 COOH terminus through its first metal-binding motif. By using scanning force microscopy and fluorescence resonance energy transfer-based experiments we provide evidence for an intramolecular interaction between the NH(2) and COOH termini of CLIP-170. This interaction interferes with the binding of the CLIP-170 to MTs. We propose that conformational changes in CLIP-170 are important for binding to dynactin, LIS1, and the MT tips.
Keywords:plus end–tracking proteins  motor protein  cytoplasmic dynein  LIS1  CLIP-115
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