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Review
. 2012 May 14;197(4):465-75.
doi: 10.1083/jcb.201112034.

Spectraplakins: master orchestrators of cytoskeletal dynamics

Kathleen C Suozzi  1 , Xiaoyang Wu, Elaine Fuchs
Affiliations
Review

Spectraplakins: master orchestrators of cytoskeletal dynamics

Kathleen C Suozzi et al. J Cell Biol. .

Abstract

The dynamics of different cytoskeletal networks are coordinated to bring about many fundamental cellular processes, from neuronal pathfinding to cell division. Increasing evidence points to the importance of spectraplakins in integrating cytoskeletal networks. Spectraplakins are evolutionarily conserved giant cytoskeletal cross-linkers, which belong to the spectrin superfamily. Their genes consist of multiple promoters and many exons, yielding a vast array of differential splice forms with distinct functions. Spectraplakins are also unique in their ability to associate with all three elements of the cytoskeleton: F-actin, microtubules, and intermediate filaments. Recent studies have begun to unveil their role in a wide range of processes, from cell migration to tissue integrity.

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Figures

Figure 1.
Figure 1.
Mammalian and invertebrate spectraplakin isoforms. Seven types of functional domains can be found in this family of proteins: a calponin-type actin-binding domain composed of CH1 and CH2 regions, a plakin domain, an α-helical spectrin repeat domain, PRDs, plectin repeats, an EF hand, and a GAR domain. The BPAG1a2 isoform contains a sequence coding for a highly conserved N-terminal transmembrane domain (TMD), and BPAG1a3 contains a sequence coding for a conserved myristoylation (myr) motif. BPAG1b, BPAG1e, and MACF1b contain a variable number of PRDs. PRDs are grouped into three classes termed A, B, and C, which are connected by a linker subdomain. The number of spectrin repeats and plectin repeats shown here are descriptive in nature and, in reality, vary between the spectraplakins. The structures shown of MACF1c and Shot B are predicted domain structures. Please note that this figure is not drawn to scale.
Figure 2.
Figure 2.
The binding partners of full-length ACF7/MACF1. A schematic diagram that shows multiple domains of the full-length ACF7/MACF1 and their functions. ACF7/MACF1 binds to F-actin at the N-terminal CH actin-binding domain. F-actin binding of ACF7/MACF1 mediates FA turnover and keratinocyte migration in epidermal wound repair. ACF7/MACF1 links actin with rapsyn, which anchors Ach receptors to the actin cytoskeleton. The plakin domain has been shown to have weak MT-binding activity. EF-hand Ca2+-binding activity is responsible for ACF7/MACF1 binding to MT +TIP protein EB1 and, along with GAR domain, mediates ACF7/MACF1 binding to MTs. The C terminus contains the phosphorylation site of GSK3-β. ACF7/MACF1 binding to MTs is important for targeting MTs to FAs. Phosphorylation of ACF7/MACF1 uncouples MT binding. Coordination of ACF7/MACF1 binding to MTs is important for polarizing epithelial stem cells in wound repair.
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