Rab, Arf, and Arl-Regulated Membrane Traffic in Cortical Neuron Migration

Abstract

The migration of projection neurons from its birthplace in the subventricular zone to their final destination in the cortical plate is a complex process that requires a series of highly coordinated cellular events. Amongst the key factors involved in the processes are modulators of cytoskeletal dynamics, as well as cellular membrane traffic. Members of the small GTPases family responsible for the latter process, the Rabs and Arfs, have been recently implicated in cortical neuron migration. Rab5 and Rab11, which are key modulators of endocytosis and endocytic recycling respectively, ensure proper surface expression and distribution of N-cadherin, a key adhesion protein that tethers migrating neurons to the radial glia fiber tracts during pia-directed migration. Rab7, which is associated with lysosomal biogenesis and function, is important for the final step of terminal translocation when N-cadherin is downregulated by lysosomal degradation. Arf6 activity, which is known to be important in neuronal processes outgrowth, may negatively impact the multipolar-bipolar transition of cortical neurons undergoing radial migration, but the downstream effector of Arf6 in this regard is not yet known. In addition to the above, members of the Arl family which have been recently shown to be important in radial glia scaffold formation, would also be important for cortical neuron migration. In this short review, we discuss recent advances in our understanding of the importance of membrane traffic regulated by the Rab, Arf, and Arl family members in cortical neuron migration.

Knock-down of Hdj2/DNAJA1 co-chaperone results in an unexpected burst of tumorigenicity of C6 glioblastoma cells

“…Rab7 deficient cells had increased total cellular level of N-cadherin, which is consistent with a decrease lysosomal degradation of protein. Rab1 deficiency caused an accumulation of N-cadherin in cytoplasmic vesicles [ 42 , 44 ]. As a co-chaperone and apart its chaperonic function Hdj2 is able to bind cellular proteins and Rabs proteins could be among its partners.…”

Rabs, Membrane Dynamics, and Parkinson's Disease

“…Roles for Rabs and their regulators/effectors in neurological and neurodevelopmental disorders are also known, and a subset of Rabs and related small GTPases of the ARF family have roles in cortical neuron migration during corticogenesis (Tang, ). Defects in cell soma membrane traffic, polarized axonal/dendritic transport, as well as bidirectional axonal transport are both causes as well as consequences of neurodegenerative diseases (Schweitzer et al, ; Tang, ; Ikenaka et al, ; Schreij et al, ).…”

Zika virus as a causative agent for primary microencephaly: the evidence so far

“…The authors found that ZIKV targets the radial glial cells of fetuses. Another particularly important group among the infected cells were those of the dorsal ventricular zone of the developing cortex, where NPCs that give rise to cells that will eventually migrate and populate the cerebral cortex originate (Bystron et al 2008;Tang 2016). ZIKV infection markedly reduced the numbers of these progenitor cells and, consequentially resulted in a quantifiably smaller cortical area (Wu et al 2016).…”

“…In this regard, a particularly important cell type in the fetal brain that is targeted by ZIKV is the radial glial cells, which are key regulators of cerebral cortex development (Borrell and Götz 2014). Other than being progenitor cells, these cells serve as a tissue scaffold for the migration of cortical neurons from the ventricular/subventricular zone to the cortical surface in the generation of the laminar structure of the mammalian cortex (Rakic 2007;Molnár and Clowry 2012;Tang 2016). A recent report has highlighted the prominent expression of a putative ZIKV entry receptor AXL receptor tyrosine kinase (Corno et al 2016) in radial glia cells, as well as in astrocytes and NPCs of multiple mammalian species (Nowakowski et al 2016).…”