title: Recruitment of dynein to late endosomes and lysosomes through light intermediate chains.
abstract: Cytoplasmic dynein is involved in a wide range of cellular processes, but how it is regulated and how it recognizes an extremely wide range of cargo are incompletely understood. The dynein light intermediate chains, LIC1 and LIC2 (DYNC1LI1 and DYNC1LI2, respectively), have been implicated in cargo binding, but their full range of functions is unknown. Using LIC isoform-specific antibodies, we report the first characterization of their subcellular distribution and identify a specific association with elements of the late endocytic pathway, but not other vesicular compartments. LIC1 and LIC2 RNA interference (RNAi) each specifically disrupts the distribution of lysosomes and late endosomes. Stimulation of dynein-mediated late-endosomal transport by the Rab7-interacting lysosomal protein (RILP) is reversed by LIC1 RNAi, which displaces dynein, but not dynactin, from these structures. Conversely, expression of ΔN-RILP or the dynactin subunit dynamitin each fails to displace dynein, but not dynactin. Thus, using a variety of complementary approaches, our results indicate a novel specific role for the LICs in dynein recruitment to components of the late endocytic pathway.
authors.affiliation: Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Serena C
authors.initials: SC
authors.lastname: Tan
authors.forename: Julian
authors.initials: J
authors.lastname: Scherer
authors.forename: Richard B
authors.initials: RB
authors.lastname: Vallee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D056445:Cytoplasmic Dyneins / Q000235:genetics / Q000378:metabolism*; D000072159:Dynactin Complex; D011992:Endosomes / Q000378:metabolism*; D055785:Gene Knockdown Techniques / Q000379:methods; D006367:HeLa Cells; D006801:Humans; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D020409:Molecular Motor Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D051381:Rats; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C000606361:DCTN2 protein, human; D000072159:Dynactin Complex; D052118:Lysosomal-Associated Membrane Protein 1; D008869:Microtubule-Associated Proteins; D020409:Molecular Motor Proteins; C423317:RILP protein, human; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; C000716466:rab7 GTP-binding proteins, rat; C424131:DYNC1LI1 protein, human; D056445:Cytoplasmic Dyneins; C548808:DYNC1LI2 protein, human; D020691:rab GTP-Binding Proteins