Keratin function and regulation in tissue homeostasis and pathogenesis

Abstract

Epithelial tissues act as hubs in metabolism and communication and protect the organism against dehydration, infections, pharmacological and physical stress. Keratin intermediate filament proteins are well established as major cytoskeletal players in maintaining epithelial integrity. More recently, an involvement of keratins in growth control and organelle functions has emerged. Disruption of the keratin cytoskeleton by mutations or its reorganization following posttranslational modifications can render epithelia susceptible to tissue damage and various stresses, while loss of keratin expression is a hallmark of epithelial-mesenchymal transition (EMT). To understand the molecular mechanisms by which keratins perform their functions remains a formidable challenge. Based on selected examples, we will discuss how cell-specific expression of keratin isotypes affects cytoarchitecture and cell behavior. Further, we ask how posttranslational modifications alter keratin organization and interactions during signaling. Next, we discuss pathomechanisms of epidermal keratin disorders in the light of novel data. Finally, we raise open questions and point out future directives.

A keratin scaffold regulates epidermal barrier formation, mitochondrial lipid composition, and activity

“…Recent genetic and biochemical data established a major role of keratins in cytoarchitecture, cell adhesion, cell growth, and regulation of distinct immune functions ( Kim et al, 2006 ; Vijayaraj et al, 2009 ; Kim and Coulombe, 2010 ; Wallace et al, 2012 ; Roth et al, 2012a , b ; Lessard et al, 2013 ; Chung et al, 2015 ).…”

mTOR (Mammalian Target of Rapamycin): Hitting the Bull’s Eye for Enhancing Neurogenesis After Cerebral Ischemia?

“…56 The mTOR activity in the mTORC1 complex is regulated through phosphorylation of its specific residues at C-terminal, predominantly on serine 2448, the target of Akt and p70S6K. [57][58][59] The phosphorylated AKT (Ser473) phosphorylates PRAS40 and dissociates its binding to Raptor, thus facilitating mTORC1 activation by stopping mTORC1 from being inhibited by PRAS40. 60,61 Then mTORC1 phosphorylates its downstream target p70S6K at threonine 389 residue, which is critical for p70S6K activation and widely recognized as a parameter for mTORC1 activity.…”

A Kaleidoscope of Keratin Gene Expression and the Mosaic of Its Regulatory Mechanisms

“…The widest spectrum of keratin expression is inherent to the hair follicle and the nail bed. The expression pattern of keratin has been well described and characterized [ 2 , 3 , 4 ]. Dysfunctions of tissues and organs due to violations of keratin distribution could be associated with impaired control of the keratin expression or genetic abnormalities.…”