It would be interesting to see if spatiotemporal katanin-mediated MT severing and depolymerization are employed to regulate growth cone migration and directional responses to guidance cues (Figure 2). Like many of the actin regulatory proteins, the exact effects of MT severing on neurons can be complex and may

depend on a number of factors such as how the MT is posttranslationally modified and what other MT-binding proteins are present. For example, severing of stable MTs enables the release of short MTs from the centrosomal region for their transport BMS-754807 cost down the axon and organized into the dense MT array in the axonal shaft (Yu et al., 2005). Local severing of MT arrays has been Proteases inhibitor shown to be involved in the formation of collateral braches, a process that may involve the local creation of dynamic MT plus ends (Yu et al., 2008). In nerve growth cones, MT severing has been observed to break down the looped MTs that are often associated with stalled growth cones (Dent et al., 1999 and Schaefer et al., 2002). Finally, very limited attention has been given to the minus ends of MTs. Both axons and dendrites contain microtubule fragments with exposed minus ends. Surprisingly,

these minus ends undergo little depolymerization, indicating the existence of a mechanism that caps and stabilizes them (Dammermann et al., 2003). It is of interest to know that KIF2 localizes to both plus and minus ends for

depolymerization. Therefore, protecting the minus ends could have a larger impact on axonal growth and guidance than one might think. Cell-cell and cell-matrix adhesions are macromolecular protein complexes that provide a direct linkage between the cell and its external environment. They are essential for tissue morphogenesis and cell migration. During brain development, adhesion molecules provide an important roadmap, and together with secreted cues, guide axonal and dendritic growth to form the neural circuitry (Kamiguchi, 2007, Kolodkin and Tessier-Lavigne, 2011, Maness and Schachner, 2007 and Myers et al., 2011). In growth cones, adhesions can be derived from several different receptors including integrins, cadherins, and the immunoglobin superfamily (IgSF) members. In neurons adhesions often appear as small, punctate structures and are referred Calpain to as point contacts. The ligands for integrins are found in the extracellular matrix, while cadherins and IgSF proteins interact homophillically with molecules expressed on the surface of adjacent cells (Kolodkin and Tessier-Lavigne, 2011). Following receptor activation at the plasma membrane, intracellular adhesion components are recruited to the nascent contact, providing the platform needed for chemical and force-based adhesive signaling events (Huttenlocher and Horwitz, 2011). A popular model to describe how adhesions modulate motility is the “molecular clutch.