Scientific background: |
RAB5A(Ras-associated protein RAB5A), also called RAB5, is a protein that in humans is encoded by
the RAB5A gene. RAB5 is a rate-limiting component of the machinery regulating the kinetics of
membrane traffic in the early endocytic pathway. The RAB5A gene is mapped on 3p24.3. Tuberin
functions as a RAB5GAP in vivo to negatively regulate RAB5-GTP activity in endocytosis. Ectopically
expressed ALS2 localized with RAB5 and early endosome antigen-1 onto early endosomal
compartments and stimulated the enlargement of endosomes in cultured cortical neurons. RAB5 is
indispensable for a form of receptor tyrosine kinase-induced actin remodeling called circular
ruffling. RAB5 signals to the actin cytoskeleton through RNTRE, a RAB5-specific GTPase-activating
protein (GAP). RAB5 activity on phagosome membranes began to increase on disassembly of the actin
coat encapsulating phagosomes. RAB5 activation was either continuous or repetitive for up to 10
minutes, but it ended before the collapse of engulfed apoptotic cells. Expression of a dominant-negative
mutant of RAB5 delayed this collapse of apoptotic thymocytes, showing a role for RAB5 in phagosome
maturation. |
References: |
1. Bucci, C., Parton, R. G., Mather, I. H., Stunnenberg, H., Simons, K., Hoflack, B., Zerial, M. The small
GTPase rab5 functions as a regulatory factor in the early endocytic pathway. Cell 70: 715-728,
1992.
2. Kitano, M., Nakaya, M., Nakamura, T., Nagata, S., Matsuda, M. Imaging of Rab5 activity identifies
essential regulators for phagosome maturation. Nature 453: 241-245, 2008.
3. Lanzetti, L., Rybin, V., Malabarba, M. G., Christoforidis, S., Scita, G., Zerial, M., Di Fiore, P. P. The
Eps8 protein coordinates EGF receptor signalling through Rac and trafficking through Rab5. Nature
408: 374-377, 2000. |