042 | The GTPase Rab21 is required for neuronal development and migration in the cerebral cortex

Cellular and Molecular Neurobiology

Author: Yael Macarena Peralta Cuasolo | Email: macafcq@gmail.com

Yael Macarena Peralta Cuasolo , Sebastián Dupraz , Nicolas Usain 3°4°, Mariano Bisbal 3°5°, Gonzalo Quassollo , Mauricio R Galiano , Diego Grassi , Santiago Quiroga , Lucas Javier Sosa

1° Departamento de Química Biológica Ranwell Caputto, Facultad de Ciencias Químicas, CIQUIBIC-CONICET-Universidad Nacional de Córdoba, Córdoba, Argentina
2° Axonal Growth and Regeneration, German Center for Neurodegenarative Diseases, Bonn, Germany
3° Instituto de Investigación Médica Mercedes y Martín Ferreyra (INIMEC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Córdoba, Córdoba, Argentina
4° Centro de Biología Celular y Molecular (CeBiCeM, FCEFyN-UNC), Facultad de Ciencias Exactas Físicas y Naturales, Universidad Nacional de Córdoba, Córdoba, Argentina
5° Instituto Universitario Ciencias Biomédicas de Córdoba (IUCBC), Córdoba, Argentina

The development of the complex structure of the mammalian neocortex requires the
proper migration of developing neurons from the ventricular zone containing neural
progenitors to the cortical plate. The precise coordination of different cellular processes
such as cytoskeleton dynamics, membrane trafficking and cell adhesion during
migration is achieved by a variety of signaling pathways. GTPases play a central role in
all these processes. The small GTPase Rab21 regulates migration and neurite growth in
developing neurons. Moreover, regulators and effectors of Rab21 have been implicated
in brain pathologies with cortical malformations, suggesting a key function for the
Rab21 signaling pathway in cortical development. Mechanistically, it has been posited
that Rab21 influences cell migration by controlling the trafficking of endocytic vesicles
containing adhesion molecules. However, direct evidence of the participation of Rab21
or its mechanism of action in the regulation of cortical migration is still incomplete. In
this study, we demonstrate that Rab21 plays a critical role in the differentiation and
migration of pyramidal neurons by regulating the levels of the amyloid precursor
protein on the neuronal cell surface. Rab21 loss of function increased the levels of
membrane-exposed APP, resulting in impaired cortical neuronal differentiation and