Keratins: a structural scaffold with emerging functions

Abstract

Intermediate filament proteins form an essential part of the cytoskeleton and provide topological order to cells and tissues. These features result from their intrinsic property of self-organization and their response to extrinsic cues. Keratins represent the largest subgroup among all intermediate filament proteins and are differentially expressed as pairs of type I and type II intermediate filament proteins in epithelia. Their primary function is to impart mechanical strength to cells. This function is illustrated by patients with keratin mutations and by gene-deficient mice. Additional functions include their participation in the response to stress, cell signalling and apoptosis, and thus the keratin cytoskeleton appears far more dynamic than previously anticipated. This may result from hyperphosphorylation and possibly from interaction with associated proteins. How signalling networks affect keratin organization, turnover and function and vice versa will be a major challenge for future investigations.

Clumping Factor B, a Fibrinogen-binding MSCRAMM (Microbial Surface Components Recognizing Adhesive Matrix Molecules) Adhesin of Staphylococcus aureus, Also Binds to the Tail Region of Type I Cytokeratin 10

“…Along with actin microfilaments and microtubules, the IF constitute the cy-toskeleton of vertebrate epithelial cells (13). Their primary function is to provide mechanical strength to cells (13,14).…”

“…Along with actin microfilaments and microtubules, the IF constitute the cy-toskeleton of vertebrate epithelial cells (13). Their primary function is to provide mechanical strength to cells (13,14). On the basis of differences in molecular weight and pI, cytokeratins can be divided into two types: type II keratins that include K1, K5, and K6 and are generally more basic and larger (53-67 kDa) than the type I molecules, and K10 and K14 -K17 (40 -63 kDa).…”

Downregulation of cytokeratin 18 is associated with paclitaxel-resistance and tumor aggressiveness in prostate cancer

“…Although the recognized function of cytokeratins, in general, has been defined historically as structural because of their interactions with the extracellular matrix and their role in cell-cell contact and adhesion (27), these structurally related proteins also influence protein synthesis and modulate intracellular cytokine signaling cascades (28). Some authors have observed the association of downregulation of CK18 with anticancer drug resistance.…”

Decreased levels of keratin 8 sensitize mice to streptozotocin‐induced diabetes

“…Keratins are well‐known stress proteins that are rapidly regulated both through changes in expression levels and through post‐translational modifications, such as phosphorylation and glycosylation, in response to cell stress or injury 32, 33. However, also during normal physiological processes including cell movement and division, keratins are actively assembled, disassembled and remodelled in the cells 34.…”