EHD2 mediates trafficking from the plasma membrane by modulating Rac1 activity

Benjamin, Sigi; Weidberg, Hilla; Rapaport, David; Pekar, Olga; Nudelman, Marina; Segal, Daniel; Hirschberg, Koret; Katzav, Shulamit; Ehrlich, Marcelo; Horowitz, Mia

doi:10.1042/bj20111010

Cited by 29 publications

(25 citation statements)

References 59 publications

(60 reference statements)

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“…Overexpression of PAST1 had a dominant negative effect, showing approximately 50–60% attenuation in endocytosis (Fig 10). A similar dominant negative effect has also been previously shown in HeLa cells overexpressing the mammalian EHD2, leading to attenuation of plasma membrane internalization [45]. …”

Section: Discussionsupporting

confidence: 75%

Past1 Modulates Drosophila Eye Development

et al. 2017

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Endocytosis is a multi-step process involving a large number of proteins, both general factors, such as clathrin and adaptor protein complexes, and unique proteins, which modulate specialized endocytic processes, like the EHD proteins. EHDs are a family of Eps15 Homology Domain containing proteins that consists of four mammalian homologs, one C. elegans, one Drosophila melanogaster and two plants orthologs. These membrane-associated proteins are involved in different steps of endocytic trafficking pathways. We have previously shown that the Drosophila EHD ortholog, PAST1, associates predominantly with the plasma membrane. Mutations in Past1 result in defects in endocytosis, male sterility, temperature sensitivity and premature death of the flies. Also, Past1 genetically interacts with Notch. In the present study, we investigated the role of PAST1 in the developing fly eye. In mutant flies lacking PAST1, abnormal differentiation of photoreceptors R1, R6 and R7 was evident, with partial penetrance. Likewise, five cone cells were present instead of four. Expression of transgenic PAST1 resulted in a dominant negative effect, with a phenotype similar to that of the deletion mutant, and appearance of additional inter-ommatidial pigment cells. Our results strongly suggest a role for PAST1 in differentiation of photoreceptors R1/R6/R7 and cone cells of the fly ommatidia.

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Section: Discussionsupporting

confidence: 75%

Past1 Modulates Drosophila Eye Development

et al. 2017

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“…How these genes integrally coordinate to promote cell growth remains unclear. A plasma-membrane-associated protein, EHD2, is found to regulate trafficking from the plasma membrane by controlling Rho GTPases activity (37). EHD proteins are also able to bind to phospholipids in plasma membrane (38, 39) and form complexes with IGF-1R to regulate downstream Akt pathway (40).…”

Section: Discussionmentioning

confidence: 99%

Identification of gene regulation patterns underlying both oestrogen- and tamoxifen-stimulated cell growth through global gene expression profiling in breast cancer cells

Fan

Cunliffe

Agboke

et al. 2014

European Journal of Cancer

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Purpose A c-Src inhibitor blocks estrogen (E2)-induced stress and converts E2 responses from inducing apoptosis to growth stimulation in E2-deprived breast cancer cells. A reprogrammed cell line, MCF-7:PF, results in a functional estrogen receptor (ER). We addressed the question of whether the selective ER modulator 4-hydroxytamoxifen (4-OHT) could target ER to prevent E2-stimulated growth in MCF-7:PF cells. Methods Expression of mRNA was measured through real-time RT-PCR. Global gene expression profile was analyzed through microarray. Transcriptome profiles were screened by RNA-sequencing. Results Unexpectedly, both 4-OHT and E2 stimulated cell growth in a concentration-dependent manner. Expression profiling showed a remarkable overlap in genes regulated in the same direction by E2 and 4-OHT. Pathway enrichment analysis of the 280 genes commonly deregulated in MCF-7:PF cells by 4-OHT and E2 revealed functions mainly related to membrane, cytoplasm, and metabolic processes. Further analysis of 98 genes up-regulated by both 4-OHT and E2 uncovered a significant enrichment in genes associated with membrane remodeling, cytoskeleton reorganization, cytoplasmic adapter proteins, cytoplasm organelles proteins, and related processes. 4-OHT was more potent than E2 in up-regulating some membrane remodeling molecules, such as EHD2, FHL2, HOMER3 and RHOF. In contrast, 4-OHT acted as an antagonist to inhibit expression of the majority of enriched membrane-associated genes in wild-type MCF-7 cells. Conclusions Long-term selection pressure has changed the cell population responses to 4-OHT. Membrane-associated signaling is critical for 4-OHT-stimulated cell growth in MCF-7:PF cells. This study provides a rationale for the further investigation of target therapy for tamoxifen resistant patients.

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“…EHDs (EH (Eps15 homology)-domain-containing proteins) participate in different stages of endocytosis. EHD2 is a plasma membrane-associated EHD which regulates trafficking from the plasma membrane and recycling [15]. The EH domain of plant EHDs bears 32 % homology to the mammalian EHDs EH domain but also regulates endocytosis [16].…”

Section: Discussionmentioning

confidence: 99%

Effects of EHD2 interference on migration of esophageal squamous cell carcinoma

Yang

Zhang

et al. 2013

Med Oncol

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C-Terminal EH domain-containing protein 2 (EHD2) of the EHD family is associated with plasma membrane. We investigated the expression of EHD2 in human esophageal squamous cell carcinoma (ESCC) and the EHD2 expression to study the therapeutic effect of chemotherapy drugs. Western blot and immunohistochemistry were used to measure the expression of EHD2 protein in ESCC and adjacent normal tissue in 98 patients. EHD2 protein level was reduced in ESCC tissues in comparison with adjacent normal tissues. Under-expression of EHD2 increased the motility property of ESCC cell TE1 in vitro by wound-healing assays and transwell migration assays, and it was concurrent with the decreased expression of epithelial marker E-cadherin. Under-expression of EHD2 in TE1 can cause resistance to cisplatin. Our results suggested that EHD2 low expression is involved in the pathogenesis of ESCC, and it might be a favorable independent poor prognostic parameter for ESCC.

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EHD2 mediates trafficking from the plasma membrane by modulating Rac1 activity

Cited by 29 publications

References 59 publications

Past1 Modulates Drosophila Eye Development

Past1 Modulates Drosophila Eye Development

Identification of gene regulation patterns underlying both oestrogen- and tamoxifen-stimulated cell growth through global gene expression profiling in breast cancer cells

Effects of EHD2 interference on migration of esophageal squamous cell carcinoma

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