Self-organization of keratin intermediate filaments into cross-linked networks.
Keratins, the largest subgroup of intermediate filament (IF) proteins, form a network of 10-nm filaments built from type I/II heterodimers in epithelial cells. A major function of keratin IFs is to protect epithelial cells from mechanical stress. Like filamentous actin, keratin IFs must be cross-linked in vitro to achieve the high level of mechanical resilience characteristic of live cells. Keratins 5 and 14 (K5 and K14), the main pairing occurring in the basal progenitor layer of epidermis and related epithelia, can readily self-organize into large filament bundles in vitro and in vivo. Here, we show that filament self-organization is mediated by multivalent interactions involving distinct regions in K5 and K14 proteins. Self-organization is determined independently of polymerization into 10-nm filaments, but involves specific type I-type II keratin complementarity. We propose that self-organization is a key determinant of the structural support function of keratin IFs in vivo.
Lee
Chang-Hun
CH
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Coulombe
Pierre A
PA
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007382:Intermediate Filaments / Q000737:chemistry / Q000378:metabolism; D053547:Keratin-14 / Q000302:isolation & purification / Q000378:metabolism*; D053555:Keratin-5 / Q000302:isolation & purification / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D017385:Sequence Homology
D053547:Keratin-14; D053555:Keratin-5