Figure 7.

Proposed role of BICD1 in H_CT trafficking. In wild type motor neurons, H_CT binds to plasma membrane receptors, which include polysialogangliosides and is internalized at synaptic sites located in the periphery (1); note that for clarity, internalization of H_CT along the axon and in the soma is not shown. H_CT and neurotrophin-receptor complexes are sorted to signaling endosomes (2), which are retrogradely transported by cytoplasmic dynein (3), toward the cell soma. Here, they associate with somatic sorting endosomes (4) decorated by sorting nexin 1 (SNX1) and other retromer components. Neurotrophin receptors are then trafficked toward MVB/lysosomes (5) for degradation, whilst H_CT is recycled to the plasma membrane (6). Impairment of the lysosomal targeting of TrkB and other proteins, including H_CT receptors, in neurons lacking BICD1 is envisaged to mainly redirect them to the recycling route back to the plasma membrane. The main consequence of these miss-sorting steps is an increase in H_CT binding sites and neurotrophin receptors (Terenzio et al., 2014) on the cell surface at steady state.