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doi: 10.1242/10.1242/jcs.00157


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The `Spectraplakins': cytoskeletal giants with characteristics of both spectrin and plakin families

Katja Röper, Stephen L. Gregory and Nicholas H. Brown*

Wellcome Trust/Cancer Research UK Institute and Dept of Anatomy, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR, UK



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Fig. 1. The spectrin protein superfamily. Depicted is a selection of members of the spectrin family of proteins, comparing human and fly orthologues for each member, and in the case of spectraplakins showing both mammalian genes (MACF1 and BPAG1). The spectrin family members are arranged in a phylogenetic tree on the basis of the sequences of their calponin-homology type actin-binding domains. Protein domains detected by SMART analysis are shown in coloured boxes (Schultz et al., 1998Go).

 


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Fig. 2. The plakin protein superfamily. Depicted are all known members of the plakin family of proteins containing the plakin domain, arranged in a phylogenetic tree on the basis of the sequences of plakin domains (blue bar). Protein domains detected by SMART analysis are shown in coloured boxes (Schultz et al., 1998Go).

 


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Fig. 3. Spectraplakin gene structure, splicing and protein isoforms. The Drosophila shot gene and the human BPAG1 gene are shown. The arrows above the line show the alternative starts of transcription (P2, P1, P3, Pe). Exons are indicated by boxes, and splicing is only shown for the alternative starts or where exons are bypassed. Different alternative transcripts are then shown below each gene. The colours of the alternative N-termini are random, but the colours of the other exons reflect the protein domains encoded, as used in Figs 1 and 2. Below these is the labelling of the different domains used in the new nomenclature: the different N-termini (2,1,3,e for the very N-termini, C for each of the two calponin homology domains), the common plakin domain (p), the plectin-repeat domain (P in shot, P1 or P2 in BPAG1), the spectrin-repeat domain, EF hands and the GAS2 domain (SG). On the left is the description of each isoform using the new nomenclature. Additional variation in the GAS2 domain for both genes and in the splicing linking the plakin domain to the spectrin repeats in shot are not shown. It is not known whether all these forms exist. For example recent northern analysis could not detect BPAG1 transcripts containing the C domains with P1, or P1 with P2 (Leung et al., 2001bGo).

 


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Fig. 4. Functions of spectraplakins. Spectraplakins have at least four different known or proposed modes of function in a cell, depicted here in the Drosophila context: (1) crosslinking of cytoskeletal filaments; (2) linking the cytoskeleton to plasma membrane proteins; (3) organising the interaction between the cortical cytoskeleton and plasma membrane proteins to generate membrane subdomains; and (4) acting as a scaffold protein that recruits signalling proteins to sites of cytoskeletal activity.

 

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© The Company of Biologists Ltd 2002