QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 16, Issue 4, 1769-1776, April 2005

This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: E04-08-0739v1 16/4/1769    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Moskowitz, H. S. Articles by Ryan, T. A. Search for Related Content PubMed PubMed Citation Articles by Moskowitz, H. S. Articles by Ryan, T. A.

Highly Cooperative Control of Endocytosis by Clathrin

Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021

Submitted August 25, 2004; Revised December 28, 2004; Accepted January 17, 2005
Monitoring Editor: Keith Mostov

Clathrin assembles into a dynamic two-dimensional lattice on the plasma membrane where it plays a critical role in endocytosis. To probe the regulation of this process, we used siRNA against clathrin, in combination with single cell assays for transferrin uptake as well as total internal reflection microscopy, to examine how endocytic rates and membrane dynamics depend upon cellular clathrin concentration ([Clathrin]). We find that endocytosis is tightly controlled by [Clathrin] over a very narrow dynamic range such that small changes in [Clathrin] can lead to large changes in endocytic rates, indicative of a highly cooperative process (apparent Hill coefficient, n > 6). The number of clathrin assemblies at the cell surface was invariant over a wide range of [Clathrin]; however, both the amount of clathrin in each assembly and the subsequent membrane dynamics were steeply dependent on [Clathrin]. Thus clathrin controls the structural dynamics of membrane internalization via a strongly cooperative process. We used this analysis to show that one important regulator of endocytosis, the actin cytoskeleton, acts noncompetitively as a modulator of clathrin function.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Timothy A. Ryan (taryan{at}med.cornell.edu).

This article has been cited by other articles:

				P. D. Allaire, B. Ritter, S. Thomas, J. L. Burman, A. Yu. Denisov, V. Legendre-Guillemin, S. Q. Harper, B. L. Davidson, K. Gehring, and P. S. McPherson Connecdenn, A Novel DENN Domain-Containing Protein of Neuronal Clathrin-Coated Vesicles Functioning in Synaptic Vesicle Endocytosis J. Neurosci., December 20, 2006; 26(51): 13202 - 13212. [Abstract] [Full Text] [PDF]

				A. Hayakawa, D. Leonard, S. Murphy, S. Hayes, M. Soto, K. Fogarty, C. Standley, K. Bellve, D. Lambright, C. Mello, et al. The WD40 and FYVE domain containing protein 2 defines a class of early endosomes necessary for endocytosis PNAS, August 8, 2006; 103(32): 11928 - 11933. [Abstract] [Full Text] [PDF]

				K. D. Bellve, D. Leonard, C. Standley, L. M. Lifshitz, R. A. Tuft, A. Hayakawa, S. Corvera, and K. E. Fogarty Plasma Membrane Domains Specialized for Clathrin-mediated Endocytosis in Primary Cells J. Biol. Chem., June 9, 2006; 281(23): 16139 - 16146. [Abstract] [Full Text] [PDF]

				L. Hinrichsen, A. Meyerholz, S. Groos, and E. J. Ungewickell Bending a membrane: How clathrin affects budding PNAS, June 6, 2006; 103(23): 8715 - 8720. [Abstract] [Full Text] [PDF]

				H. Ohno Physiological Roles of Clathrin Adaptor AP Complexes: Lessons from Mutant Animals J. Biochem., June 1, 2006; 139(6): 943 - 948. [Abstract] [Full Text] [PDF]

				T. Mitsunari, F. Nakatsu, N. Shioda, P. E. Love, A. Grinberg, J. S. Bonifacino, and H. Ohno Clathrin Adaptor AP-2 Is Essential for Early Embryonal Development Mol. Cell. Biol., November 1, 2005; 25(21): 9318 - 9323. [Abstract] [Full Text] [PDF]