title: Spectrin- and ankyrin-based membrane domains and the evolution of vertebrates.
abstract: Spectrin and ankyrin are membrane skeletal proteins that contribute to mechanical support of plasma membranes and micron-scale organization of diverse membrane-spanning proteins. This chapter provides a plausible scenario for the evolution of ankyrin- and spectrin-based membrane domains with a focus on vertebrates. The analysis integrates recent phylogenetic information with functional analyses of spectrin and ankyrin in erythrocytes, axon initial segments and nodes of Ranvier in neurons, T-tubules and intercalated disks of cardiomyocytes, lateral membrane domains of epithelial cells, and costameres of striated muscle. A core spectrin-ankyrin mechanism for coordinating membrane-spanning proteins and mechanically stabilizing membrane bilayers was expanded in vertebrates by gene duplication events, insertion of giant alternately spliced exons of axonal ankyrins, and a versatile peptide-binding fold of ANK repeats that facilitated acquisition of new protein partners. Cell adhesion molecules (CAM), including dystroglycan, L1 CAM family members, and cadherins, are the earliest examples of membrane-spanning proteins with ankyrin-binding motifs and were all present in urochordates. In contrast, ion channels have continued to evolve ankyrin-binding sites in vertebrates. These considerations suggest a model where proto-domains formed through interaction of ankyrin and spectrin with CAMs. These proto-domains then became populated with ion channels that developed ankyrin-binding activity with selective pressure provided by optimization of physiological function. The best example is the axon initial segment where ankyrin-binding activity evolved sequentially and independently first in L1 CAMs, then in voltage-gated sodium channels, and finally in KCNQ2/3 channels, with the selective advantage of fast and precisely regulated signaling.
authors.affiliation: HHMI, Duke University Medical Center, Durham, North Carolina, USA; Department of Biochemistry, Duke University Medical Center, Durham, North Carolina, USA. Electronic address: benne012@mc.duke.edu.
authors.forename: Vann
authors.initials: V
authors.lastname: Bennett
authors.forename: Damaris N
authors.initials: DN
authors.lastname: Lorenzo
mesh_terms: D000818:Animals; D017487:Ankyrins / Q000737:chemistry / Q000378:metabolism*; D001369:Axons / Q000378:metabolism; D005075:Biological Evolution; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D013049:Spectrin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D017487:Ankyrins; D013049:Spectrin
keywords: Adaptive evolution; Ankyrin; Axon initial segment; Costamere; Node of Ranvier; Spectrin