Kazrin, a novel periplakin-interacting protein associated with desmosomes and the keratinocyte plasma membrane

Abstract

Periplakin forms part of the scaffold onto which the epidermal cornified envelope is assembled. The NH2-terminal 133 amino acids mediate association with the plasma membrane and bind a novel protein, kazrin. Kazrin is highly conserved and lacks homology to any known protein. There are four alternatively spliced transcripts, encoding three proteins with different NH2 termini. Kazrin is expressed in all layers of stratified squamous epithelia; it becomes membrane associated in the suprabasal layers, coincident with up-regulation of periplakin, and is incorporated into the cornified envelope of cultured keratinocytes. Kazrin colocalizes with periplakin and desmoplakin at desmosomes and with periplakin at the interdesmosomal plasma membrane, but its subcellular distribution is independent of periplakin. On transfection, all three kazrin isoforms have similar subcellular distributions. We conclude that kazrin is a novel component of desmosomes that associates with periplakin.

Dynamics and unexpected localization of the plakin binding protein, kazrin, in mouse eggs and early embryos

“…The Western blot also revealed a faint doublet, suggesting that kaz A and possibly B were present; however, because of the low amount of protein from 125 eggs, it was difficult to consistently resolve the doublet of kaz A and B. Of interest, the Western blot revealed a band at the correct molecular weight for kaz C. Previously, only kaz A and B transcripts had been identified in mice (Groot et al, 2004). To further confirm our Western results, we subjected eggs to RT-PCR using primers to each kaz A-D as well as primers that recognize all isoforms.…”

“…Recently, convincing evidence revealed a novel noncanonical plakin interacting protein, kazrin (kaz), which acts as a cytolinker protein linking periplakin to the plasma membrane in keratinocytes (Groot et al, 2004). Of interest, images in Groot et al (2004) showed evidence that kaz brings desmosomal plakins such as periplakin and desmoplakin (DP) into close proximity with actin filaments near adherens junctions implying that kaz may act as a cytolinker functionally connecting adherens junctions and desmosomes (Groot et al, 2004).…”

“…In humans, kaz was found to have four splice variants, termed kaz A-D. All are capable of binding plakins, and all contain a nuclear localizing signal (NLS), which is functional. In mice, two variants have been found in mouse expressed sequence tag databases to date, kaz A and B (Groot et al, 2004;personal searches). Since its initial discovery in keratinocytes, kaz has been found in numerous different tissue types (Groot et al, 2004).…”

“…In mice, two variants have been found in mouse expressed sequence tag databases to date, kaz A and B (Groot et al, 2004;personal searches). Since its initial discovery in keratinocytes, kaz has been found in numerous different tissue types (Groot et al, 2004). Consequently, the dual cellular localization of kaz (junctional and nuclear) and its broad spectrum of expression suggested that kaz may have multiple functions across many tissues.…”

“…Most forms of kaz have an NLS (Groot et al, 2004), and antibodies to kaz have clearly revealed kaz staining within the nuclear compartment of epidermal keratinocytes. We show here that kaz staining is also prevalent within the female pronucleus as early as 1-1.25 hr after activation (Fig.…”