Forty years on: clathrin-coated pits continue to fascinate

Abstract

Clathrin-mediated endocytosis (CME) is a fundamental process in cell biology and has been extensively investigated over the past several decades. Every cell biologist learns about it at some point during his or her education, and the beauty of this process has led many of us to go deeper and make it the topic of our research. Great progress has been made toward elucidating the mechanisms of CME, and the field is becoming increasingly complex, with several hundred new publications every year. This makes it easy to get lost in the vast amount of literature and forget about the fundamentals of the field, which are based on the careful interpretation of simple observations made >40 years ago, as exemplified by a study performed by Anderson, Brown, and Goldstein in 1977. We examine how this seminal study was pivotal to our understanding of CME and its progression into ever-increasing complexity over the past four decades.

FIGURE 1:

Key steps in our understanding of the CCV cycle. Clockwise from top: original images showing LDL-ferritin being internalized through coated structures on the surface of normal fibroblasts (Anderson et al., 1977a); SDS–PAGE gel showing clathrin and adaptor proteins purified from pig brain (Pearse, 1975); x-ray crystallography studies revealing how tyrosine-based motifs interact with AP2 (Owen and Evans, 1998); in vitro studies showing that dynamin assembles into ring structures that suggest a mechanism by which dynamin might pinch off coated pits (Hinshaw and Schmid, 1995); studies in yeast pioneering live-cell imaging to understand dynamics of endocytic patch assembly (Kaksonen et al., 2003); structured illumination imaging allowing unprecedented resolution to visualize the relationship of clathrin-coated structures (green) to the actin cytoskeleton (red; Li et al., 2015).