Periventricular Heterotopia: Shuttling of Proteins through Vesicles and Actin in Cortical Development and Disease

Figure 1

Periventricular heterotopia as a disorder of vesicle trafficking. Schematic figure illustrates the disruption of various developmental processes that give rise to features seen in PH. Disruption of filamin-ARF- (via BIG2) mediated vesicle trafficking can disrupt both caveolin-mediated endocytosis and presumably trafficking from the Golgi to the membrane. Vesicle trafficking dictates the delivery and degradation of various cell cycle proteins and thereby influences cell proliferation. Disruption of the cyclin B proteins leads to microcephaly in PH. Vesicle trafficking also alters the distribution of proteins involved in neuronal migration such as paxillin. Loss of PH impairs neuronal migration and the morphology of migratory neurons. Lastly, the loss of neuroependymal integrity giving rise to heterotopia is due to impairments in the cell adhesion along the ventricular lining. Genes that disrupt vesicle trafficking impair cell-cell adhesion and disrupt the integrity of the epithelium.