EB/RP gene family encodes tubulin binding proteins

Juwana, Jan-Peter; Henderikx, Paula; Mischo, Axel; Wadle, Andreas; Fadle, Natalie; Gerlach, Klaus; Arends, Jan Willem; Hoogenboom, Hennie R.; Pfreundschuh, Michael; Renner, Christoph

doi:10.1002/(sici)1097-0215(19990412)81:2<275::aid-ijc18>3.0.co;2-z

Cited by 77 publications

(75 citation statements)

References 22 publications

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“…APC has been shown to associate with EB1 (Su et al, 1995), a 30 kDa protein which we (Morrison et al, 1998a) and others (Berrueta et al, 1998;Juwana et al, 1999) have recently shown to be associated with microtubule tips. APC is itself a microtubule tip-associated protein (Munemitsu et al, 1994;Smith et al, 1994;NaÈ thke et al, 1996;Morrison et al, 1997), a feature ascribed to the presence of a microtubule-binding basic domain towards the Cterminus of the protein.…”

Section: Introductionmentioning

confidence: 80%

Regulation and function of the interaction between the APC tumour suppressor protein and EB1

et al. 2000

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The interaction between the adenomatous polyposis coli (APC) tumour suppressor and the microtubule-associated protein EB1 was examined. Immunoprecipitation suggested that APC and EB1 were not associated in cultures of HCT116 cells arrested in mitosis. The C-terminal 170 amino acids of APC, puri®ed as a bacterial fusion protein, precipitated EB1 from cell extracts, signi®cantly re®ning the location of the EB1 interaction domain in APC. In vitro phosphorylation of this fusion protein by either protein kinase A or p34 cdc2 reduced its ability to bind to EB1. Expression of GFP fusions to C-terminal APC sequences lacking or including the APC basic domain but encompassing the EB1 binding region in SW480 cells revealed a microtubule tip association which co-localized with that of EB1. Expression of the basic domain alone revealed a non-speci®c microtubule localization. In vitro interaction studies con®rmed that the APC basic domain did not contribute to EB1 binding. These ®ndings strongly suggest that the interaction between APC and EB1 targets APC to microtubule tips, and that the interaction between the two proteins is down-regulated during mitosis by the previously described mitotic phosphorylation of APC.

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Section: Introductionmentioning

confidence: 80%

Regulation and function of the interaction between the APC tumour suppressor protein and EB1

et al. 2000

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“…This proposed function of KRIT1 in targeting microtubules in response to external signals is reminiscent of that of EB1, another plus end microtubule-binding protein. EB1 binds to the tumor suppressor adenomatosis polyposis coli (APC), and it has been proposed that the activity of the Wnt signaling pathway is involved in the regulation of this interaction and the consequent targeting of microtubules (37).…”

Section: Discussionmentioning

confidence: 99%

KRIT1 , a gene mutated in cerebral cavernous malformation, encodes a microtubule-associated protein

Günel

Laurans

Shin

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

111

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Mutations in Krev1 interaction trapped gene 1 (KRIT1) cause cerebral cavernous malformation, an autosomal dominant disease featuring malformation of cerebral capillaries resulting in cerebral hemorrhage, strokes, and seizures. The biological functions of KRIT1 are unknown. We have investigated KRIT1 expression in endothelial cells by using specific anti-KRIT1 antibodies. By both microscopy and coimmunoprecipitation, we show that KRIT1 colocalizes with microtubules. In interphase cells, KRIT1 is found along the length of microtubules. During metaphase, KRIT1 is located on spindle pole bodies and the mitotic spindle. During late phases of mitosis, KRIT1 localizes in a pattern indicative of association with microtubule plus ends. In anaphase, the plus ends of the interpolar microtubules show strong KRIT1 staining and, in late telophase, KRIT1 stains the midbody remnant most strongly; this is the site of cytokinesis where plus ends of microtubules from dividing cells overlap. These results establish that KRIT1 is a microtubule-associated protein; its location at plus ends in mitosis suggests a possible role in microtubule targeting. These findings, coupled with evidence of interaction of KRIT1 with Krev1 and integrin cytoplasmic domain-associated protein-1 alpha (ICAP1 ␣), suggest that KRIT1 may help determine endothelial cell shape and function in response to cell-cell and cell-matrix interactions by guiding cytoskeletal structure. We propose that the loss of this targeting function leads to abnormal endothelial tube formation, thereby explaining the mechanism of formation of cerebral cavernous malformation (CCM) lesions. C erebral cavernous malformation (CCM) is a disease affecting brain vasculature. Characteristic lesions affect capillaries and have grossly dilated vascular channels lined by only a single layer of endothelium without normal vessel wall elements such as smooth muscle or intervening neural parenchyma (1). The nature of these lesions suggests an abnormality in normal development of these capillaries; however, the mechanism of their occurrence and an explanation for their focal nature have remained elusive.The aberrant channels in CCM lesions are fragile, commonly resulting in intracranial hemorrhage. Clinical signs and symptoms are largely determined by the size and location of the hemorrhage, and range from incidental findings on MRI (Fig. 1) to rare catastrophic cerebral hemorrhage resulting in death. The disease has been recognized as a common clinical entity because of the advent of MRI (2). Both MRI and autopsy studies suggest a prevalence of cavernous malformation up to 0.5%, although only 20-30% of affected individuals develop symptomatic disease (3-8).Symptomatic patients typically present in the third through the fifth decades of life (3) with headaches, seizures, or focal neurological deficits. Treatment ranges from therapy with anti-epileptic drugs in patients with seizures, to surgical excision of accessible lesions in patients who suffer from hemorrhage or intractable seizures (9-13).Si...

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“…Proteins homologous to EB1 have been identified in many organisms from yeast to human and have been shown to interact with MT plus-ends (6,(12)(13)(14)(15). EB1 binding to MTs is independent of APC, but APC targeting to MT plus-ends requires EB1 (16,17).…”

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confidence: 99%

Crystal Structure of the Amino-terminal Microtubule-binding Domain of End-binding Protein 1 (EB1)

Hayashi

Ikura

2003

Journal of Biological Chemistry

170

145

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The end-binding protein 1 (EB1) family is a highly conserved group of proteins that localizes to the plusends of microtubules. EB1 has been shown to play an important role in regulating microtubule dynamics and chromosome segregation, but its regulation mechanism is poorly understood. We have determined the 1.45-Å resolution crystal structure of the amino-terminal domain of EB1, which is essential for microtubule binding, and show that it forms a calponin homology (CH) domain fold that is found in many proteins involved in the actin cytoskeleton. The functional CH domain for actin binding is a tandem pair, whereas EB1 is the first example of a single CH domain that can associate with the microtubule filament. Although our biochemical study shows that microtubule binding of EB1 is electrostatic in part, our mutational analysis suggests that the hydrophobic network, which is partially exposed in our crystal structure, is also important for the association. We propose that, like other actin-binding CH domains, EB1 employs the hydrophobic interaction to bind to microtubules.

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EB/RP gene family encodes tubulin binding proteins

Cited by 77 publications

References 22 publications

Regulation and function of the interaction between the APC tumour suppressor protein and EB1

Regulation and function of the interaction between the APC tumour suppressor protein and EB1

KRIT1 , a gene mutated in cerebral cavernous malformation, encodes a microtubule-associated protein

Crystal Structure of the Amino-terminal Microtubule-binding Domain of End-binding Protein 1 (EB1)

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