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NEED TO ENDOCYTOSE? ABL TO HELP pp. 93-113 $100.00
Authors:  M. Jacob, The Wistar Institute, Philadelphia, PA, USA
Abstract:
Cells use various mechanisms to internalize substances presented in their surroundings, with pinocytosis, phagocytosis, macropinocytosis, caveolae/raft-dependent endocytosis, and receptor-mediated clathrin-dependent endocytosis being the most extensively studied. Pinocytosis occurs independently of actin polymerization. In contrast, the importance of F-actin remodeling during internalization by the other mechanisms is well established. Similarly, the key role of membrane-proximal tyrosine kinases during internalization of small receptor ligands such as growth factors, or much larger bacteria, is undeniable. Surprisingly though, the molecular mechanisms linking tyrosine kinase activation and cytoskeletal reorganization pathways to endocytosis are not completely understood. cAbl is a member of the only family of tyrosine kinases known to date to have an actin-binding domain that allows them to interact with both globular and filamentous actin [1-7] and yet, our understanding of its role in endocytosis is still in its infancy. Herein, I review the evidence supporting a role for cAbl in the uptake of ligated receptors, apoptotic cells, bacteria and viruses. Specifically, I describe and discuss cAbl-dependent pathways involved in 1) clathrin-mediated endocytosis of two different receptors (EGFR and BCR), 2) caveolin-dependent endocytosis of viruses, and 3) macropinocytosis of bacteria and apoptotic cells, highlighting the overlap and differences between them. Finally, I discuss the potential significance of having specific endocytic mechanisms adapted to given conditions, as well as the significance of cAbl‘s role in endocytosis linked to physiological signal transduction and pathological conditions such as cancer and fibrosis. 


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NEED TO ENDOCYTOSE? ABL TO HELP pp. 93-113