Spectraplakin family proteins – cytoskeletal crosslinkers with versatile roles

Abstract

The different cytoskeletal networks in a cell are responsible for many fundamental cellular processes. Current studies have shown that spectraplakins, cytoskeletal crosslinkers that combine features of both the spectrin and plakin families of crosslinkers, have a critical role in integrating these different cytoskeletal networks. Spectraplakin genes give rise to a variety of isoforms that have distinct functions. Importantly, all spectraplakin isoforms are uniquely able to associate with all three elements of the cytoskeleton, namely, F-actin, microtubules and intermediate filaments. In this Review, we will highlight recent studies that have unraveled their function in a wide range of different processes, from regulating cell adhesion in skin keratinocytes to neuronal cell migration. Taken together, this work has revealed a diverse and indispensable role for orchestrating the function of different cytoskeletal elements in vivo.

Portrait of glial scar in neurological diseases

“…The cytoskeletons of astrocytes are highly changeable; they have a strong potential to quickly remodel themselves to cooperate with the normal development of morphogenesis and tissue injury. 4 IF proteins are a part of the structure of cytoskeletal networks that affect morphology and mortality. 4 Furthermore, these proteins are also tightly associated with reactive gliosis in glial scar formation.…”

“… 4 IF proteins are a part of the structure of cytoskeletal networks that affect morphology and mortality. 4 Furthermore, these proteins are also tightly associated with reactive gliosis in glial scar formation. Compared to the quiescent state of astrocytes, the expression of glial fibrillary astrocytic protein (GFAP), which is the astrocyte-specific IF protein, as well as vimentin and nestin, is up-regulated in reactive astrocytes, causing hypertrophy via reorganizing the cytoskeleton of these cells.…”

The plakin domain of C. elegans VAB-10/plectin acts as a hub in a mechanotransduction pathway to promote morphogenesis

“…VAB-10 and plectin belong to the spectraplakin family, which are large proteins linking different cytoskeleton networks. They include an N-ter actin-binding domain (calponin homology); a plakin domain consisting of up to nine spectrin repeats (SR) with an atypical Src-homology 3 (SH3) domain found within the central SR, either multiple spectrin or plectin repeats; and a C-ter microtubule-binding domain (Zhang et al, 2017). Each SR comprises three α-helices; the SH3 domain bulges out of the loop connecting the second and third α-helices of SR5 (Choi and Weis, 2011;Ortega et al, 2011).…”

The plakin domain ofC. elegansVAB-10/plectin acts as a hub in a mechanotransduction pathway to promote morphogenesis

“…As outlined above, VAB-10A is a strong mechanosensor candidate as it is the only conserved hemidesmosome protein between C. elegans and vertebrates (Zhang and Labouesse, 2010a). Additionally, proteins of the plakin and spectraplakin families such as vertebrate desmoplakin, plectin and MACF/ACF7, Drosophila Shot and C. elegans VAB-10 contain in their plakin domain up to nine spectrin repeats (SR) (Zhang et al, 2017), which are domains known to unfold in vitro under mechanical stress (Law et al, 2003;Lenne et al, 2000) (note that vab-10 produces two major isoforms through alternative splicing, VAB-10A/plectin and VAB-10B/MACF, which have the plakin domain in common, see below) (Bosher et al, 2003). Furthermore, the central SR harbors a predicted SH3 domain, which could potentially mediate protein-protein interactions (Fig.…”