Clathrin-independent endocytosis, retrograde trafficking, and cell polarity

Abstract

Several mechanisms allow for cargo internalization into cells within membrane-bound endocytic carriers. How these internalization processes couple to specific pathways of intracellular distribution remains poorly explored. Here, we review uptake reactions that are independent of the conventional clathrin machinery. We discuss how these link to retrograde trafficking from endosomes to the Golgi apparatus and exemplify biological situations in which the polarized secretion capacity of the Golgi apparatus allows for retrograde cargoes to be delivered to specialized areas of the plasma membrane, such as the leading edge of migratory cells or the immunological synapse of immune cells. We also address the evidence that allows to position apicobasal polarity of epithelial cells in this context. The underlying theme is thereby the functional coupling between specific types of endocytosis to intracellular retrograde trafficking for protein cargoes that need to be localized in a highly polarized and dynamic manner to plasmalemmal subdomains.

Membrane Rafts: Portals for Viral Entry

“…Clathrin-independent endocytosis (CIE) pathways ( Mayor et al, 2014 ; Sandvig et al, 2018 ; Shafaq-Zadah et al, 2020 ) are cholesterol-sensitive mechanisms that may be classified into caveolae-mediated endocytosis (dynamin-dependent) and non-clathrin non-caveolae mediated endocytosis, which can be dynamin-dependent ( VanHamme et al, 2008 ) or independent ( Damm et al, 2005 ). Caveolae ( Bastiani and Parton, 2010 ; Cheng and Nichols, 2016 ) are the best characterized microdomains of membrane rafts, which consist of small plasma membrane invaginations at the surface of several mammalian cell types.…”

Non-permissive human conventional CD1c+dendritic cells enabletrans-infection of human primary renal tubular epithelial cells and protect BK polyomavirus from neutralization

“…Further work is needed to establish the molecular determinants of such differences between non-immune and immune cells like cDC. A recent review pointed out the link between the CLIC/GEEC endocytosis and glycosphingolipids (GSL) which encompass gangliosides in the establishment of cell polarity (72). DC polarization leading to the formation of a synapse is an important event in T cell priming (see for review (84)) but might also be crucial in the BKPyV trans-infection process we described here.…”

“…Although not proven here, it is tempting to speculate that a similar entry pathway for BKPyV occurs in CD1c-sorted cDC. This compartment was identified as CLIC/GEEC vesicles whose formation is clathrin-independent (see for review (72)). Interestingly, BKPyV was shown to infect hRPTEC in a clathrin-and caveolinindependent manner indicating that some BKPyV entry steps might be common between those cells and cDC (73,74).…”

Retrograde And Anterograde Transport Of LAT-Vesicles During The Immunological Synapse Formation: Defining The Finely-Tuned Mechanism

“…LAT, which has been shown to be present in cholesterol-rich domains of the plasma membrane 54 , may be internalized in a clathrin-independent manner. Of note, in a recent review, Shafaq-Zadah et al have pointed several links between the retrograde pathway and the mechanism of endocytosis that do not depend on the conventional clathrin machinery 55 . It would thus be important to characterize the endocytic pathways followed by LAT in resting and activated conditions as recently done for the TCR 56 .…”