We thank S. Butler, E. Carpenter, J. Feldman, D. Geschwind, A.

Kania, S. Price, M. Sofroniew, for experimental instruction and helpful discussions; M. Cilluffo Rucaparib datasheet and the UCLA Brain Research Institute Electron Microscope Core; J. Briscoe, S. Butler, G. Konopka, J. Sanes, and S. Price for comments on the manuscript; M. Cayouette, J. Muhr, and S. Sockanathan for reagents. We acknowledge W. Filipiak, T. Sauders, and the Transgenic Animal Model Core of the University of Michigan’s Biomedical Research Core Facilities for the preparation of the Foxp4LacZ mice. This work was supported by the Broad Center for Regenerative Medicine and Stem Cell Research at UCLA, and grants to B.G.N. from the Whitehall Foundation (2004-05-90-APL), the Muscular Dystrophy Association (92901), and the NINDS (NS053976 and NS072804). D.L.R. was supported by the UCLA Training Program in Neural Repair (NIH T32 NS07449). C.A.P. was supported by the UCLA-California Institute for Regenerative Medicine Training Grant (TG2-01169). A.M.G. and C.P.-C. were supported by a grant from the NIMH (MH083785). S.L. and E.E.M. were supported by a grant from the NIH (HL071589).

“
“The dynein-dynactin complex is the major minus-end-directed microtubule (MT) motor for vesicle transport in eukaryotic cells. While the dynein motor alone is capable of producing Lenvatinib solubility dmso Adenylyl cyclase force in vitro, the dynactin complex is a necessary

cofactor for motor function in cells (Schroer, 2004). How dynactin contributes to dynein function remains unclear. The p150Glued subunit of dynactin interacts directly with the dynein motor (Karki and Holzbaur, 1995 and Vaughan and Vallee, 1995) and also independently binds MTs and MT plus-end binding proteins, including EB1 and EB3, via interactions mediated by the N-terminal cytoskeleton-associated protein glycine-rich (CAP-Gly) domain (Akhmanova and Steinmetz, 2008, Ligon et al., 2003 and Waterman-Storer et al., 1995). These observations led to the hypothesis that the direct binding of dynactin to the MT enhances the processivity of dynein during transport (Waterman-Storer et al., 1995). This hypothesis is supported by in vitro biophysical studies showing that dynactin increases run lengths and enhances processivity at the single motor level (King and Schroer, 2000 and Ross et al., 2006). However, recent studies in non-neuronal cells show that the CAP-Gly domain of p150Glued is not necessary for normal dynein-mediated transport and localization of organelles including peroxisomes, lysosomes, and Golgi in either HeLa or S2 cells (Dixit et al., 2008 and Kim et al., 2007). In yeast as well, the CAP-Gly domain of dynactin is not required for processive motility by dynein (Kardon et al.