Abstract
One of the most fundamental processes of the cell is the uptake of molecules from the surrounding environment. Clathrin-mediated endocytosis (CME) is the best-described uptake pathway and regulates nutrient uptake, protein and lipid turnover at the plasma membrane (PM), cell signaling, cell motility and cell polarity. The main protein in CME is clathrin, which assembles as a triskelion-looking building block made of three clathrin heavy chains and three clathrin light chains. Compared to clathrin heavy chains (CHCs), the role of the two isoforms of clathrin light chains (CLCA and CLCB) is poorly understood. Here, we confirm that the simultaneous deletion of both CLCA/B causes abnormal actin structures at the ventral PM and we describe them, for the first time, as functional invadopodia rather than disorganized actin-cytoskeleton assembly sites. Their identification is based on the occurrence of common invadopodia markers as well as functional invadopodia activity characterized by an increased local proteolytic activity of the extracellular matrix proteins. We demonstrate that CLCA/B deletion impacts the intracellular trafficking and recovery of the matrix metalloproteinase 14 (MMP14) leading to its accumulation at the plasma membrane and induction of invadopodia formation. Importantly, we show that invadopodia formation can be prevented by depletion of MMP14. As such, we propose that CLCA/B regulate invadopodia formation by regulating MMP14 delivery to the plasma membrane.
Highlights
Uptake of biomolecules from the extracellular environment is the most fundamental cellular process
In was calculated from 14 (WT) cells, both clathrin light chain A (CLCA) and clathrin light chain B (CLCB) were detectable whereas only CLCB and CLCA were detectable in CLCA−/− and CLCB−/− cells, respectively (Figure 1A)
Our results show that deletion of both CLCA and CLCB impairs the intracellular recycling of the matrix metalloproteinase matrix metalloproteinase 14 (MMP14), promoting its accumulation at the cell plasma membrane
Summary
Uptake of biomolecules from the extracellular environment is the most fundamental cellular process. Clathrin-mediated endocytosis (CME) is the most important and best characterized endocytic pathway and regulates nutrient uptake, protein and lipid turnover at the plasma membrane, cell signaling, cell motility and cellular polarity [1,2,3]. CME is a very complex process that relies on the coordinated recruitment of multiple proteins to initiate the formation of a clathrin-coated pit (CCP) at the plasma membrane, which will drive membrane invagination and lead to the release of clathrin-coated vesicles (CCVs) into the cytosol [4,5]. CHCs are fundamental for CME as they form the structural backbone of the triskelia while CLCs appear to usually be dispensable for CME [6,7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
