Phocein: A potential actor in vesicular trafficking at Purkinje cell dendritic spines.

Phocein is an intracellular protein highly expressed in neurons. It is the major partner of the striatin family members which are scaffolding proteins involved in signaling and trafficking. Due to its association with dynamin via direct interactions with nucleotide diphosphate kinase (NDPK) and EPS15, phocein has been implicated in vesicular trafficking, acting in particular in the endocytic process. This review focuses on immuno-cytochemical studies showing the strict localization of phocein in Purkinje cell dendritic spines involved in excitatory transmission in the cerebellum of postnatal and adult rodents. Immunogold labeling sometimes detects phocein in close vicinity with endocytic-like membrane profiles suggesting that phocein plays a role in endocytosis. Furthermore, co-localization of phocein and SG2NA within spines suggests that their interactions have a functional significance in the molecular cascades that underly membrane trafficking in post-synaptic structures. As the striatin family members are highly concentrated in dendritic spines, their interactions with phocein might be involved in mediating synaptic plasticity through spine remodeling by endocytosis.

Survival of interneurons and parallel fiber synapses in a cerebellar cortex deprived of Purkinje cells: studies in the double mutant mouse Grid2Lc/+;Bax(-/-).

The Lurcher mutation in the Grid2 gene causes the cell autonomous death of virtually all cerebellar Purkinje cells and the target-related death of 90% of the granule cells and 60-75% of the olivary neurons. Inactivation of Bax, a pro-apoptotic gene of the Bcl-2 family, in heterozygous Lurcher mutants (Grid2Lc/+) rescues approximately 60% of the granule cells, but does not rescue Purkinje or olivary neurons. Given the larger size of the cerebellar molecular layer in Grid2Lc/+;Bax(-/-) double mutants compared to Grid2Lc/+ mutants, we analyzed the survival of the stellate and basket interneurons as well as the synaptic connectivity of parallel fibers originating from the surviving granule cells in the absence of their Purkinje cell targets in the Grid2Lc/+;Bax(-/-) cerebellum. Quantification showed a significantly higher density of interneurons ( approximately 60%) in the molecular layer of the Grid2Lc/+;Bax(-/-) mice compared to Grid2Lc/+, suggesting that interneurons are subject to a BAX-dependent target-related death in the Lurcher mutants. Furthermore, electron microscopy showed the normal ultrastructural aspect of a number of parallel fibers in the molecular layer of the Grid2Lc/+; Bax(-/-) double mutant mice and preserved their numerous synaptic contacts on interneurons, suggesting that interneurons could play a trophic role for axon terminals of surviving granule cells. Finally, parallel fibers varicosities in the double mutant established "pseudo-synapses" on glia as well as displayed autophagic profiles, suggesting that the connections established by the parallel fibers in the absence of their Purkinje cell targets were subject to a high turnover involving autophagy.