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.

Clathrin-adaptor ratio and membrane tension regulate the flat-to-curved transition of the clathrin coat during endocytosis

“…The complex coordination of CCS formation during CME has been investigated for decades 32 , 33 and the field has been driven by the competition between the constant curvature versus the constant area models 13 . Recent technological advances, in particular in CLEM, favoured the constant area model 19 .…”

Cargo regulates clathrin-coated pit invagination via clathrin light chain phosphorylation

“…Clathrin-mediated endocytosis (CME) is a major pathway that controls receptor uptake from the plasma membrane and is essential for physiological processes including synaptic vesicle recycling, developmental signaling, and immune responses ( McMahon and Boucrot, 2011 ; Mettlen et al, 2018 ). A triskelion is composed of three units of clathrin heavy chain, each associated with a clathrin light chain (CLC; Brodsky, 2012 ; Maib et al, 2017 ). Clathrin triskelia assemble onto the plasma membrane to form clathrin-coated pits (CCPs), which trap receptor cargoes and invaginate, becoming spherical clathrin-coated vesicles (CCVs) that are pinched off and deliver their cargoes into the cell ( Lampe et al, 2016 ; Kaksonen and Roux, 2018 ).…”

MicroRNAs Regulating Cytoskeleton Dynamics, Endocytosis, and Cell Motility—A Link Between Neurodegeneration and Cancer?

“…Among all types of cellular transport, CME is currently the best characterized process that has been extensively studied since its discovery in 1964 [reviewed in Maib et al ( 63 ) and Mettlen et al ( 64 )]. Numerous ligands, including transferrin and epithelial growth factor (EGF), coupled to the corresponding receptors are internalized via CME.…”