Search for inhibitors of endocytosis: Intended specificity and unintended consequences - PubMed (original) (raw)

Search for inhibitors of endocytosis: Intended specificity and unintended consequences

Dipannita Dutta et al. Cell Logist. 2012.

Abstract

We discuss here the variety of approaches that have been taken to inhibit different forms of endocytosis. Typically, both non-specific and specific chemical inhibitors of endocytosis are tried in order to "classify" entry of a new plasma membrane protein into one of the various types of endocytosis. This classification can be confirmed through genetic approaches of protein depletion or overexpression of mutants of known endocytosis machinery components. Although some new compounds have been designed to be selective in biochemical assays, we caution investigators to be alert to the unintended consequences that sometimes arise when these compounds are applied to intact cells.

Keywords: chemical inhibitor; clathrin-independent endocytosis; clathrin-mediated endocytosis; endocytosis; inhibitor; phagocytosis; pinocytosis.

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Figure 1. Different types of endocytosis. Endocytosis can be broadly classified into pinocytosis and phagocytosis. Phagocytosis involves the internalization of large particles like bacteria whereas macropinocytosis involves the internalization of enlarged fluid-filled endosomes; both processes are driven by actin (shown as hatched lines). Clathrin-mediated endocytosis (CME) is a selective mechanism whereby cell surface proteins containing specific sorting sequences are gathered into membrane depressions by associating with adaptor proteins which recruit clathrin (*). CME endosomes pinch off from the cell surface by recruiting the dynamin GTPase (•) to the bud neck. Clathrin-independent endocytosis (CIE) is shown here as one form, although there are reports of distinct variations of CIE. Most CIE is clathrin- and dynamin-independent and cholesterol-dependent and includes both the CLIC/GEEC and Arf6-associated forms of CIE. In addition other CIE modes (caveolae- and RhoA-dependent) are dynamin-dependent.

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