title: Mutually exclusive cytoplasmic dynein regulation by NudE-Lis1 and dynactin.
abstract: Cytoplasmic dynein is responsible for a wide range of cellular roles. How this single motor protein performs so many functions has remained a major outstanding question for many years. Part of the answer is thought to lie in the diversity of dynein regulators, but how the effects of these factors are coordinated in vivo remains unexplored. We previously found NudE to bind dynein through its light chain 8 (LC8) and intermediate chain (IC) subunits (1), the latter of which also mediates the dynein-dynactin interaction (2). We report here that NudE and dynactin bind to a common region within the IC, and compete for this site. We find LC8 to bind to a novel sequence within NudE, without detectably affecting the dynein-NudE interaction. We further find that commonly used dynein inhibitory reagents have broad effects on the interaction of dynein with its regulatory factors. Together these results reveal an unanticipated mechanism for preventing dual regulation of individual dynein molecules, and identify the IC as a nexus for regulatory interactions within the dynein complex.
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, New York 10032, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: McKenney
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Weil
authors.forename: Julian
authors.initials: J
authors.lastname: Scherer
authors.forename: Richard B
authors.initials: RB
authors.lastname: Vallee
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D056445:Cytoplasmic Dyneins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000072159:Dynactin Complex; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D051381:Rats
chemical_list: D018797:Cell Cycle Proteins; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; C525094:Nde1 protein, human; C531336:Nde1 protein, mouse; D009419:Nerve Tissue Proteins; C516550:Pafah1b1 protein, rat; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human; C513190:Pafah1b1 protein, mouse; C427758:DYNLL1 protein, human; D056445:Cytoplasmic Dyneins