Neuronal Roles of the Bicaudal D Family of Motor Adaptors

All cell types rely on active intracellular cargo transport to shuttle essential cellular components such as proteins, lipids, RNA, and even organelles from the center to the periphery and vice versa. Additionally, several signaling pathways take advantage of intracellular transport to propagate their signals by moving activated receptors and protein effectors to specific locations inside the cell. Neurons particularly, being a very polarized cell type, are highly dependent on molecular motors for the anterograde and retrograde delivery of essential cellular components and signaling molecules. For these reasons, motor adaptor proteins have been extensively investigated in regard to their role in physiology and pathology of the nervous system. In this chapter, we will concentrate on a family of motor adaptor proteins, Bicaudal D (BICD), and their function in the context of the nervous system. BicD was originally described as essential for the correct localization of maternal mRNAs in Drosophila's oocyte and a regulator of the Golgi to ER retrograde transport in mammalian cells. Both mammalian BICD1 and BICD2 are highly expressed in the nervous system during development, and their importance in neuronal homeostasis has been recently under scrutiny. Several mutations in BICD2 have been linked to the development of neuromuscular diseases, and BICD2 knockout (KO) mice display migration defects of the radial cerebellar granule cells. More in line with the overall topic of this book, BICD1 was identified as a novel regulator of neurotrophin (NT) signaling as its deletion leads to defective sorting of ligand-activated NT receptors with dramatic consequences on the NT-mediated signaling pathway.