The desmosome as a model for lipid raft driven membrane domain organization

• Authors: Stephanie E Zimmer, Emory University; Andrew Kowalczyk, Emory University
• Journal Title: BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
• Volume: Volume 1862, Number 9
• Publisher: ELSEVIER | 2020-09-01, Pages 183329-183329
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.bbamem.2020.183329
• Subjects: Chemistry, Biochemistry; Biology, Cell
• Keywords: Science & Technology; Life Sciences & Biomedicine; Biochemistry & Molecular Biology; Biophysics; Desmosome; Intercellular junction; Lipid raft; Cadherin; Keratin; Skin disease; PROTEIN-KINASE-C; PLASMA-MEMBRANE; PLAKOGLOBIN-BINDING; TIGHT JUNCTIONS; ALPHA-CATENIN; CELL-ADHESION; MICE LACKING; TRANSMEMBRANE DOMAIN; CYTOPLASMIC DOMAIN; BILAYER THICKNESS

Abstract

Desmosomes are cadherin-based adhesion structures that mechanically couple the intermediate filament cytoskeleton of adjacent cells to confer mechanical stress resistance to tissues. We have recently described desmosomes as mesoscale lipid raft membrane domains that depend on raft dynamics for assembly, function, and disassembly. Lipid raft microdomains are regions of the plasma membrane enriched in sphingolipids and cholesterol. These domains participate in membrane domain heterogeneity, signaling and membrane trafficking. Cellular structures known to be dependent on raft dynamics include the post-synaptic density in neurons, the immunological synapse, and intercellular junctions, including desmosomes. In this review, we discuss the current state of the desmosome field and put forward new hypotheses for the role of lipid rafts in desmosome adhesion, signaling and epidermal homeostasis. Furthermore, we propose that differential lipid raft affinity of intercellular junction proteins is a central driving force in the organization of the epithelial apical junctional complex.