Osteoclasts seeded on either glass coverslips or apatite pellets have at least two morphologically distinct substrate adhesion sites: actin-based adhesion structures including podosome belts and sealing zones, and adjacent clathrin sheets. Clathrin-coated structures are exclusively localized at the podosome belts and sealing zone, in both of which the plasma membrane forms a tight attachment to the substrate surface. When cultured on apatite osteoclasts can degrade the apatite leading to the formation of resorption lacunae. The sealing zone divides the ventral membrane into different domains, outside and inside of the sealing zones. The former facing the smooth-surfaced intact apatite contains relatively solitary or networks of larger flat clathrin structures; and the latter, facing the rough-surfaced degraded apatite in the resorption lacunae contain clathrin in various shapes and sizes. Clathrin assemblies on the membrane domain facing not only a resorption lacuna, or trails but also intact apatite indeed were observed to be heterogeneous in size and intensity, suggesting that they appeared to follow variations in the surface topography of the apatite surface. These results provide a detailed insight into the flat clathrin sheets that have been suggested to be the sites of adhesion and mechanosensing in co-operation with podosomes.
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http://dx.doi.org/10.1016/j.yexcr.2020.112433 | DOI Listing |
IUCrJ
March 2025
RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, USA.
2D template matching (2DTM) can be used to detect molecules and their assemblies in cellular cryo-EM images with high positional and orientational accuracy. While 2DTM successfully detects spherical targets such as large ribosomal subunits, challenges remain in detecting smaller and more aspherical targets in various environments. In this work, a novel 2DTM metric, referred to as the 2DTM p-value, is developed to extend the 2DTM framework to more complex applications.
View Article and Find Full Text PDFElife
January 2025
Institute of Parasitology, Faculty of Agricultural and Environmental Sciences, McGill University, Montreal, Canada.
Paramyxovirus membrane fusion requires an attachment protein for receptor binding and a fusion protein for membrane fusion triggering. Nipah virus (NiV) attachment protein (G) binds to ephrinB2 or -B3 receptors, and fusion protein (F) mediates membrane fusion. NiV-F is a class I fusion protein and is activated by endosomal cleavage.
View Article and Find Full Text PDFNat Commun
December 2024
Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.
Int J Mol Sci
November 2024
Department of Bionano Technology, Gachon Medical Research Institute, Gachon University, Seongnam 13120, Republic of Korea.
Alzheimer's disease (AD) is a complex neurodegenerative disorder influenced by various genetic factors. In addition to the well-established amyloid precursor protein (), Presenilin-1 (), Presenilin-2 (), and apolipoprotein E (), several other genes such as Sortilin-related receptor 1 (), Phospholipid-transporting ATPase ABCA7 (), Triggering Receptor Expressed on Myeloid Cells 2 (), Phosphatidylinositol-binding clathrin assembly protein (), and clusterin () were implicated. These genes contribute to neurodegeneration through both gain-of-function and loss-of-function mechanisms.
View Article and Find Full Text PDFCell Rep
December 2024
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address:
During clathrin-mediated endocytosis (CME), dozens of proteins are recruited to nascent CME sites on the plasma membrane, and their spatial and temporal coordination is crucial for efficient CME. Here, we show that the scaffold protein intersectin1 (ITSN1) promotes CME by organizing and stabilizing endocytic protein interaction networks. Live-cell imaging of genome-edited cells revealed that endogenously labeled ITSN1 is recruited during CME site stabilization and growth and that ITSN1 knockdown impairs endocytic protein recruitment during this stage.
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