Role of the actin-binding protein profilin1 in radial migration and glial cell adhesion of granule neurons in the cerebellum

Abstract

Profilins are small G-actin-binding proteins essential for cytoskeletal dynamics. Of the four mammalian profilin isoforms, profilin1 shows a broad expression pattern, profilin2 is abundant in the brain, and profilin3 and profilin4 are restricted to the testis. In vitro studies on cancer and epithelial cell lines suggested a role for profilins in cell migration and cell-cell adhesion. Genetic studies in mice revealed the importance of profilin1 in neuronal migration, while profilin2 has apparently acquired a specific function in synaptic physiology. We recently reported a mouse mutant line lacking profilin1 in the brain; animals display morphological defects that are typical for impaired neuronal migration. We found that during cerebellar development, profilin1 is specifically required for radial migration and glial cell adhesion of granule neurons. Profilin1 mutants showed cerebellar hypoplasia and aberrant organization of cerebellar cortex layers, with ectopically arranged granule neurons. In this commentary, we briefly introduce the profilin family and summarize the current knowledge on profilin activity in cell migration and adhesion. Employing cerebellar granule cells as a model, we shed some light on the mechanisms by which profilin1 may control radial migration and glial cell adhesion. Finally, a potential implication of profilin1 in human developmental neuropathies is discussed.