Membrane traffic during axon development

Abstract

Brain formation requires the establishment of complex neural circuits between a diverse array of neuronal subtypes in an intricate and ever changing microenvironment and yet with a large degree of specificity and reproducibility. In the last three decades, mounting evidence has established that neuronal development relies on the coordinated regulation of gene expression, cytoskeletal dynamics, and membrane trafficking. Membrane trafficking has been considered important in that it brings new membrane and proteins to the plasma membrane of developing neurons and because it also generates and maintains the polarized distribution of proteins into neuronal subdomains. More recently, accumulating evidence suggests that membrane trafficking may have an even more active role during development by regulating the distribution and degree of activation of a wide variety of proteins located in plasma membrane subdomains and endosomes. In this article the evidence supporting the different roles of membrane trafficking during axonal development, particularly focusing on the role of SNAREs and Rabs was reviewed. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1185-1200, 2016.

cAMP‐induced activation of protein kinase A and p190B RhoGAP mediates down‐regulation of TC10 activity at the plasma membrane and neurite outgrowth

“…(ii) dbcAMP‐induced TC10 inactivation was mediated by PKA in PC12 cells, (iii) p190B depletion efficiently reduced cAMP‐induced down‐regulation of TC10 and RhoA, and severely hampered cAMP‐induced neurite outgrowth in PC12 cells, (iv) p190B was specifically recruited to the plasma membrane upon dbcAMP treatment in PC12 cells, and (v) dbcAMP‐induced TC10 inactivation was dependent on STEF and Rac1. The importance of coordinated regulation between membrane trafficking and cytoskeletal reorganization in axon/neurite outgrowth has been emphasized in recent published reports (Pfenninger, ; Wojnacki & Galli, ), and we believe that the signaling pathway shown here, cAMP‐PKA‐STEF‐Rac1‐p190B‐TC10/RhoA (Figure c), is a plausible mechanism for this type of coordination.…”

Regulation of plasma membrane expansion during axon formation

“…The trafficking of membrane components is an essential step for axon growth and differentiation. It involves organelles of the exocytic pathway, such as the rough endoplasmic reticulum (RER) and the Golgi apparatus (Bentley & Banker, ; Wojnacki and Galli, ), as well as endosomes (Villarroel‐Campos et al, ; Wojnacki and Galli, ). At the trans Golgi network (TGN), or eventually at recycling endosomes (RE), axonal membrane proteins are sorted and packed into appropriate carriers.…”

“…At the trans Golgi network (TGN), or eventually at recycling endosomes (RE), axonal membrane proteins are sorted and packed into appropriate carriers. After budding and exiting from the TGN, tubulo‐vesicular carriers are shipped away toward the plasma membrane by MT‐based transport (Bentley and Banker, ; Wojnacki and Galli, ). The final step of this journey is the delivery of the transported cargoes into the plasma membrane by exocytosis, and event referred as membrane addition and that entails membrane expansion (Pfenninger, ).…”

“…From this location cargos can either traffic to late endosomes (LE) and lysosomes (Lys) for degradation or recycle directly to the plasma membrane; they may also shuttle to RE for subsequent delivery to the plasma membrane. In neurons, endosomal pathways are involved in many important physiological processes such as receptor recycling, intracellular signalling (Yap and Winckler, ) and membrane turnover (Hausott and Klimaschewski, ) and therefore play a decisive role in axonal growth and differentiation (Tojima and Kamiguchi, ; Villarroel‐Campos et al, ,b; Wojnacki and Galli, ).…”

“…Major components of the cellular machinery and signaling pathways involved in axon/dendrite formation have been identified (Arimura and Kaibuchi, 2007;Schelski and Bradke, 2017). These studies have established that cytoskeletal assembly (Conde and C aceres, 2009;Kapitein and Hoogenraad, 2015;van Beuningen and Hoogenraad, 2016) and membrane protein trafficking (Horton and Ehlers, 2003;Bentley and Banker, 2016;Wojnacki and Galli, 2016) are two key events underlying the generation of axons and dendrites. Microtubule (MT)-microfilament (MF) organization, dynamics and its regulation by extrinsic and intrinsic factors, both in developing and mature neurons, have been the subject of several excellent reviews and won't be considered here (Arimura and Kaibuchi, 2007;Conde and C aceres, 2009;Van Beuningen and Hoogenraad, 2016;Jones and Svitkina, 2016;Schelski and Bradke, 2017).…”