“…Endocytosis is perturbed by the overexpression of dominant-negative Arf1, Cdc42, Arf6 and Rac1, and these mutant proteins provide a useful means of differentiating between different endocytic mechanisms under specific conditions of cell type and GTPase expression level (Kumari and Mayor, 2008;Lamaze et al, 2001;Naslavsky et al, 2004;Sabharanjak et al, 2002). However, extrapolation to more general conclusions about the specific involvement of any of these GTPases in just one type of endocytosis is hampered by reports of different effects in different experiments -for example, overexpression of mutants of Arf6 blocks both uptake via clathrincoated pits and a clathrin-independent endocytic pathway (D' SouzaSchorey et al, 1995;Naslavsky et al, 2004;Palacios et al, 2002), and overexpression of mutant Cdc42 blocks clathrin-independent uptake of GPI-linked proteins under some conditions (Sabharanjak et al, 2002) but can also perturb clathrin-mediated uptake of E-cadherin (Izumi et al, 2004) and macropinocytosis (Amstutz et al, 2008;Dharmawardhane et al, 1997;Garrett et al, 2000). The identification of effectors downstream of small GTPases that regulate different types of endocytosis, and an understanding of how such effectors mediate vesicle formation, would clearly be a major step forward.…”