Microtubule motor proteins play important roles in a very diverse range of biological functions. Recent work from our lab has revealed contributions by cytoplasmic dynein and kinesins to neurogenesis and neuronal migration during embryonic rat brain development. We found cytoplasmic dynein and its regulators LIS1, Nde1, Ndel1 to be responsible for apical nuclear migration in Radial Glial Progenitor cells (RGPs), and the kinesin Kif1a to be responsible for basal nuclear migration. Inhibition of dynein regulatory genes blocked apical nuclear migration and mitotic entry in the RGP cells, leading to microcephaly. Inhibition of Kif1a also causes microcephaly. In this case knockdown or mutation of the motor protein decreased the ratio of asymmetric:symmetric RGP divisions, and interfered with BDNF-mediated neuronal migration, which, strikingly, could be rescued in brain slice preparations by BDNF application (2). In separate studies, we have identified a novel role in cultured neurons for a cytoplasmic dynein adaptor protein in autophagosome biogenesis and transport. The adaptor, furthermore, is activated by mTOR inhibition. Our results suggest that, in response to cellular stress, the adaptor catalyzes autophagosome biogenesis and then transports mature autophagosomes and autophagolysosomes to the cell body. The adapter appears to represent the first mTOR‑regulated link between the autophagy and motor protein pathways.
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