The Spectrin-Based Membrane Skeleton and Micron-Scale Organization of the Plasma Membrane

Bennett, Vann; Gilligan, Diana M.

doi:10.1146/annurev.cb.09.110193.000331

Cited by 455 publications

(339 citation statements)

References 109 publications

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“…Certain cytoskeleton proteins, such as ankyrin, are known to be involved in regulating a variety of cellular activities (Bennett 1992; Bennett and Gilligan 1993; Bourguignon 1996; Bourguignon et al 1998a; De Matteis and Morrow 1998). Both ankyrin1 (ANK1) and ankyrin 3 (ANK3) have been shown to be expressed in breast tumor cells (Bourguignon et al 1998b, Bourguignon et al 1999).…”

Section: Resultsmentioning

confidence: 99%

“…Ankyrin belongs to a family of cytoskeletal proteins that mediate linkage of integral membrane proteins with the spectrin-based skeleton in regulating a variety of biological activities (Bennett 1992; Bennett and Gilligan 1993; De Matteis and Morrow 1998). Presently, at least three ankyrin genes have been identified: ankyrin 1 (ANK1 or ankyrin R ), ankyrin 2 (ANK2 or ankyrin B), and ankyrin 3 (ANK3 or ankyrin G ) (Lambert et al 1990; Lux et al 1990; Tse et al 1991; Otto et al 1991; Peters and Lux 1993; Kordeli et al 1995; Peters et al 1995).…”

Section: Introductionmentioning

confidence: 99%

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Ankyrin–Tiam1 Interaction Promotes Rac1 Signaling and Metastatic Breast Tumor Cell Invasion and Migration

Bourguignon

Zhu

Shao

et al. 2000

The Journal of Cell Biology

116

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Tiam1 (T-lymphoma invasion and metastasis 1) is one of the known guanine nucleotide (GDP/GTP) exchange factors (GEFs) for Rho GTPases (e.g., Rac1) and is expressed in breast tumor cells (e.g., SP-1 cell line). Immunoprecipitation and immunoblot analyses indicate that Tiam1 and the cytoskeletal protein, ankyrin, are physically associated as a complex in vivo. In particular, the ankyrin repeat domain (ARD) of ankyrin is responsible for Tiam1 binding. Biochemical studies and deletion mutation analyses indicate that the 11–amino acid sequence between amino acids 717 and 727 of Tiam1 (717GEGTDAVKRS727L) is the ankyrin-binding domain. Most importantly, ankyrin binding to Tiam1 activates GDP/GTP exchange on Rho GTPases (e.g., Rac1).Using an Escherichia coli–derived calmodulin-binding peptide (CBP)–tagged recombinant Tiam1 (amino acids 393–728) fragment that contains the ankyrin-binding domain, we have detected a specific binding interaction between the Tiam1 (amino acids 393–738) fragment and ankyrin in vitro. This Tiam1 fragment also acts as a potent competitive inhibitor for Tiam1 binding to ankyrin. Transfection of SP-1 cell with Tiam1 cDNAs stimulates all of the following: (1) Tiam1–ankyrin association in the membrane projection; (2) Rac1 activation; and (3) breast tumor cell invasion and migration. Cotransfection of SP1 cells with green fluorescent protein (GFP)–tagged Tiam1 fragment cDNA and Tiam1 cDNA effectively blocks Tiam1–ankyrin colocalization in the cell membrane, and inhibits GDP/GTP exchange on Rac1 by ankyrin-associated Tiam1 and tumor-specific phenotypes. These findings suggest that ankyrin–Tiam1 interaction plays a pivotal role in regulating Rac1 signaling and cytoskeleton function required for oncogenic signaling and metastatic breast tumor cell progression.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ankyrin–Tiam1 Interaction Promotes Rac1 Signaling and Metastatic Breast Tumor Cell Invasion and Migration

Bourguignon

Zhu

Shao

et al. 2000

The Journal of Cell Biology

116

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“…The membrane-associated cytoskeleton is a twodimensional network located on the cytoplasmic surface of the plasma membrane [21][22][23][24][25][26][27][28][29]. It consists mainly of flexible rod-shaped tetramers of spectrin that are joined by actin protofilaments to form five-or sixsided polygons.…”

Section: Introductionmentioning

confidence: 99%

Spectrin's E2/E3 ubiquitin conjugating/ligating activity is diminished in sickle cells

2005

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Erythrocyte spectrin contains E2/E3 ubiquitin conjugating/ligating activity in its a subunit. Ankyrin is a target of spectrin's E2/E3 ubiquitin conjugating/ligating activity in vitro and in vivo. We compare the ubiquitination levels of ankyrin mediated by control and sickle cell spectrin using a biotinylated ubiquitin cell-free assay. Sickle cell spectrin has diminished ability to transfer ubiquitin from an intermediate spectrin-ubiquitin thioester adduct (a 0 spectrin) to ankyrin, which may be due to glutathiolation of spectrin's E2 and/ or E3 active site cysteines. There is also a diminished ability of the sickle cell ankyrin to serve as target of spectrin's E2/E3 activity, probably due to oxidative damage to ankyrin. A direct correlation exists between the a 0 /a spectrin ratio and spectrin's ability to ubiquitinate ankyrin. There is also an inverse correlation between severity of the disease and the a 0 /a spectrin ratio in SS erythrocytes. These results suggest that reduced spectrin E2/ E3 activity is an important determinant of sickle cell severity. Am. J. Hematol. 79:89-96, 2005.

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“…These results establish that betac-spectrin is essential for the normal morphology of epithelial cells, as well as for their maintenance in monolayer culture. S PV.CTRIN is an elongated actin-binding protein that is the principal component of a system of structural proteins associated with the cytoplasmic surface of plasma membranes of most metazoan cells (reviewed by Bennett and Gilligan, 1993). Spectrin is comprised of two subunits, termed alpha and beta, that are aligned side-to-side to form heterodimers, and the dimers are linked head-to-head to form tetramers.…”

mentioning

confidence: 99%

“…Beta~-spectrin is the most common type of beta subunit, and it is expressed in most vertebrate tissues (Hu et al, 1992). The structure and function of spectrin has been best characterized in mammalian erythrocytes from both in vivo and in vitro studies (Palek and Lambert, 1990;Delaunay and Dhermy, 1993;Gallagher and Forget, 1993;Bennett and Gilligan, 1993). Erythrocyte spectrin forms a membrane-associated polygonal network by the associations of spectrin with actin illaments and with integral membrane proteins through linkages with ankyrin and protein 4.1.…”

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confidence: 99%

Expression of functional domains of beta G-spectrin disrupts epithelial morphology in cultured cells.

Moorthy

Bennett

1995

The Journal of Cell Biology

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Abstract. Spectrin is a major structural protein associated with the cytoplasmic surface of plasma membranes of many types of cells. To study the functions of spectrin, we transfected Caco-2 intestinal epithelial cells with a plasmid conferring neomycin resistance and encoding either actin-binding or ankyrin-binding domains of beta~-spectrin fused with beta-galactosidase. These polypeptides, in principle, could interfere with the interaction of spectrin with actin or ankyrin, as well as block normal assembly of alpha-and betaspectrin subunits. Cells expressing the fusion proteins represented only a small fraction of neomycin-resistant cells, but they could be detected based on expression of beta-galactosidase. Cells expressing spectrin domains exhibited a progressive decrease in amounts of endogenous betac-spectrin, although alpha-spectrin was still present. Betac-spectrin-deficient cells lost epithelial cell morphology, became multinucleated, and eventually disappeared after 10-14 d in culture. Spectrin-associated membrane proteins, ankyrin and adducin, as well as the Na÷,K÷-ATPase, which binds to ankyrin, exhibited altered distributions in cells transfected with betac-spectrin domains. E-cadherin and F-actin, in contrast to ankyrin, adducin, and the Na÷,K÷-ATPase, were expressed, and they exhibited unaltered distribution in betao-spectrin-deficient cells. Cells transfected with the same plasmid encoding betagalactosidase alone survived in culture as the major population of neomycin-resistant cells, and they exhibited no change in morphology or in the distribution of spectrin-associated membrane proteins. These results establish that betac-spectrin is essential for the normal morphology of epithelial cells, as well as for their maintenance in monolayer culture. S PV.CTRIN is an elongated actin-binding protein that is the principal component of a system of structural proteins associated with the cytoplasmic surface of plasma membranes of most metazoan cells (reviewed by Bennett and Gilligan, 1993). Spectrin is comprised of two subunits, termed alpha and beta, that are aligned side-to-side to form heterodimers, and the dimers are linked head-to-head to form tetramers. Beta subunits contain most of the recognition sites of spectrin for other proteins including ankyrin, protein 4.1 actin, as well as the site for ankyrin-independent association of spectrin with membranes. Beta~-spectrin is the most common type of beta subunit, and it is expressed in most vertebrate tissues (Hu et al., 1992). The structure and function of spectrin has been best characterized in mammalian erythrocytes from both in vivo and in vitro studies (Palek and Lambert, 1990;Delaunay and Dhermy, 1993;Gallagher and Forget, 1993;Bennett and Gilligan, 1993). Erythrocyte spectrin forms a membrane-associated polygonal network by the associations of spectrin with actin illaments and with integral membrane proteins through linkages with ankyrin and protein 4.1. Defects and deficiencies in components of the spectrin-actin network result in abnormally fr...

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The Spectrin-Based Membrane Skeleton and Micron-Scale Organization of the Plasma Membrane

Cited by 455 publications

References 109 publications

Ankyrin–Tiam1 Interaction Promotes Rac1 Signaling and Metastatic Breast Tumor Cell Invasion and Migration

Ankyrin–Tiam1 Interaction Promotes Rac1 Signaling and Metastatic Breast Tumor Cell Invasion and Migration

Spectrin's E2/E3 ubiquitin conjugating/ligating activity is diminished in sickle cells

Expression of functional domains of beta G-spectrin disrupts epithelial morphology in cultured cells.

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