DMob4/Phocein Regulates Synapse Formation, Axonal Transport, and Microtubule Organization

Abstract

The monopolar spindle-one-binder (Mob) family of kinase-interacting proteins regulate cell cycle and cell morphology, and their dysfunction has been linked to cancer. Models for Mob function are primarily based on studies of Mob1 and Mob2 family members in yeast. In contrast, the function of the highly conserved metazoan Phocein/Mob3 subfamily is unknown. We identified the Drosophila Phocein homolog (DMob4) as a regulator of neurite branching in a genome-wide RNA interference screen for neuronal morphology mutants. To further characterize DMob4, we generated null and hypomorphic alleles and performed in vivo cell biological and physiological analysis. We find that DMob4 plays a prominent role in neural function, regulating axonal transport, membrane excitability, and organization of microtubule networks. DMob4 mutant neuromuscular synapses also show a profound overgrowth of synaptic boutons, similar to known Drosophila endocytotic mutants. DMob4 and human Phocein are Ͼ80% identical, and the lethality of DMob4 mutants can be rescued by a human phocein transgene, indicating a conservation of function across evolution. These findings suggest a novel role for Phocein proteins in the regulation of axonal transport, neurite elongation, synapse formation, and microtubule organization.

Cortactin-Binding Protein 2 Modulates the Mobility of Cortactin and Regulates Dendritic Spine Formation and Maintenance

“…CTTNBP2NL, a molecule sharing similarity with CTTNBP2, associates with the PP2A protein complex, which contains PP2A, striatins, Mob3, and FAM40A/B. Striatins are highly enriched at dendritic spines (Gaillard et al, 2006), and the Mob protein family has been shown to regulate synapse formation in Drosophila (Schulte et al, 2010). FAM40A and FAM40B have recently been shown to modulate the actin cytoskeleton (Bai et al, 2011).…”

Hemispheric Asymmetries: The Comparative View

“…The authors suggest that the rightward-asymmetric pathway may be related to a rightward functional lateralization of auditory spatial attention and working memory whereas the leftward-asymmetric pathway may be related to leftward functional lateralization for language, but they did not test this assumption on a behavioral level. More direct evidence comes from a combined diffusion tensor imaging tractography and functional magnetic resonance imaging study in alcoholics and healthy controls (Schulte et al, 2010) were it was observed that white matter fiber degradation in the Corpus Callosum due to alcoholism leads to an attenuated pattern of functional visuo-motor asymmetries. While these studies are only a first step, they nevertheless show that, parallel to the work that has been conducted in birds, it may indeed be a promising approach to further investigate the role of structural white matter asymmetries in the human brain in order to reveal the underlying neurophysiological processes of human functional hemispheric asymmetries.…”

Large Neurological Component to Genetic Differences Underlying Biased Sperm Use in Drosophila

“…These candidates could be potentially involved in the development of neural networks specific for sperm competition and/or they could function at the time of sperm competition. Given that knockdown of at least some of these neural genes is lethal or affects behaviors unrelated to sperm competition (e.g., locomotion behaviors that could affect courtship or mating) (Loughney et al 1989;Lloyd et al 2000;Schulte et al 2010), we chose to test a specific hypothesis: that neural genes might influence sperm competition through neurons that innervate the female reproductive tract. This approach likely underestimates the extent of contribution of these genes that we found, but is a simple, initial, and direct test of function.…”