The mechanism of activation of the actin binding protein EHBP1 by Rab8 family members

Rai, Amrita; Bleimling, Nathalie; Vetter, Ingrid R.; Goody, Roger S.

doi:10.1038/s41467-020-17792-3

Cited by 25 publications

(26 citation statements)

References 46 publications

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“…CH domain (filamin, spectrin beta chain, actinin, utrophin, plastin) [50][51][52][53][54]: High affinity actin-binding proteins such as filamin and actinin have two tandem CH domains. Although a single CH domain is not sufficient to interact with actin in some cases, some AAPs with a single CH domain (e.g., EH domain-binding protein 1) bind to actin [55,56].…”

Section: How Abps Interact With Actinmentioning

confidence: 99%

Actin-Associated Proteins and Small Molecules Targeting the Actin Cytoskeleton

Gao,

Nakamura

2022

IJMS

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Actin-associated proteins (AAPs) act on monomeric globular actin (G-actin) and polymerized filamentous actin (F-actin) to regulate their dynamics and architectures which ultimately control cell movement, shape change, division; organelle localization and trafficking. Actin-binding proteins (ABPs) are a subset of AAPs. Since actin was discovered as a myosin-activating protein (hence named actin) in 1942, the protein has also been found to be expressed in non-muscle cells, and numerous AAPs continue to be discovered. This review article lists all of the AAPs discovered so far while also allowing readers to sort the list based on the names, sizes, functions, related human diseases, and the dates of discovery. The list also contains links to the UniProt and Protein Atlas databases for accessing further, related details such as protein structures, associated proteins, subcellular localization, the expression levels in cells and tissues, mutations, and pathology. Because the actin cytoskeleton is involved in many pathological processes such as tumorigenesis, invasion, and developmental diseases, small molecules that target actin and AAPs which hold potential to treat these diseases are also listed.

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Section: How Abps Interact With Actinmentioning

confidence: 99%

Actin-Associated Proteins and Small Molecules Targeting the Actin Cytoskeleton

Gao,

Nakamura

2022

IJMS

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Section: Discussionmentioning

confidence: 88%

“…The fusion partner in our case, EHBP1, has been shown to facilitate GLUT4 transport and regulate vesicular trafficking by connecting endocytic vesicles to the actin cytoskeleton. 25 Like melanophilin, EHBP1 is also a Rab effector protein. The N-terminal C2-like (NT-C2) domain of EHBP1 binds to lipid molecules in endosomes and the plasma membrane, and the calponin homology domain (CH) interacts with actin filaments.…”

Section: Discussionmentioning

confidence: 99%

Spitz nevus with EHBP1‐ALK fusion and distinctive membranous localization of ALK

et al. 2022

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ALK rearrangements define a histopathologically distinctive yet diverse subset of Spitz tumors characterized by fusiform to epithelioid melanocytes with frequent fascicular growth and ALK overexpression. Molecularly, these tumors are characterized by fusions between ALK and a variety of gene partners, most commonly TPM3 and DCTN1. We describe an unusual case of a Spitz nevus occurring in a 13‐year‐old female that manifested ALK immunopositivity with cell membrane localization. The proliferation was polypoid and composed of elongated nests of epithelioid melanocytes with enlarged nuclei, prominent nucleoli, and abundant cytoplasm without significant atypia and lacking mitotic figures. The nevus exhibited strong and diffuse expression of p16. Targeted next‐generation RNA sequencing revealed an in‐frame EHBP1‐ALK fusion, which has been reported only once in the literature. EHBP1 encodes an adaptor protein with plasma membrane targeting potential. Together, these findings suggest that the 5′ ALK fusion partner in Spitz tumors may dictate the subcellular localization of the ALK chimeric oncoprotein. In summary, this case highlights a rare ALK fusion associated with a distinct immunohistochemical staining pattern and further expands the spectrum of ALK‐rearranged melanocytic tumors.

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“…In the GWAS analyses of the cross-sectional neurocognitive phenotypes, we observed three genome-wide significant signals, of which we consider the gene-based association with EHBP1 as the most interesting finding ( P = 1.17E-07; Table 2 , Figure 1A , and Supplementary Figure 20 ). This protein interacts with Eps15-homology domain-containing protein 1/2 (EHD1/2) that plays a central role in GLUT4 transport and couples endocytic vesicles to the actin cytoskeleton ( Rai et al, 2020 ). It is highly expressed in many tissues, including the brain, according to GTEx ( Lonsdale et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study of Alzheimer’s Disease Brain Imaging Biomarkers and Neuropsychological Phenotypes in the European Medical Information Framework for Alzheimer’s Disease Multimodal Biomarker Discovery Dataset

Homann

Osburg

Ohlei

et al. 2022

Front. Aging Neurosci.

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Alzheimer’s disease (AD) is the most frequent neurodegenerative disease with an increasing prevalence in industrialized, aging populations. AD susceptibility has an established genetic basis which has been the focus of a large number of genome-wide association studies (GWAS) published over the last decade. Most of these GWAS used dichotomized clinical diagnostic status, i.e., case vs. control classification, as outcome phenotypes, without the use of biomarkers. An alternative and potentially more powerful study design is afforded by using quantitative AD-related phenotypes as GWAS outcome traits, an analysis paradigm that we followed in this work. Specifically, we utilized genotype and phenotype data from n = 931 individuals collected under the auspices of the European Medical Information Framework for Alzheimer’s Disease Multimodal Biomarker Discovery (EMIF-AD MBD) study to perform a total of 19 separate GWAS analyses. As outcomes we used five magnetic resonance imaging (MRI) traits and seven cognitive performance traits. For the latter, longitudinal data from at least two timepoints were available in addition to cross-sectional assessments at baseline. Our GWAS analyses revealed several genome-wide significant associations for the neuropsychological performance measures, in particular those assayed longitudinally. Among the most noteworthy signals were associations in or near EHBP1 (EH domain binding protein 1; on chromosome 2p15) and CEP112 (centrosomal protein 112; 17q24.1) with delayed recall as well as SMOC2 (SPARC related modular calcium binding 2; 6p27) with immediate recall in a memory performance test. On the X chromosome, which is often excluded in other GWAS, we identified a genome-wide significant signal near IL1RAPL1 (interleukin 1 receptor accessory protein like 1; Xp21.3). While polygenic score (PGS) analyses showed the expected strong associations with SNPs highlighted in relevant previous GWAS on hippocampal volume and cognitive function, they did not show noteworthy associations with recent AD risk GWAS findings. In summary, our study highlights the power of using quantitative endophenotypes as outcome traits in AD-related GWAS analyses and nominates several new loci not previously implicated in cognitive decline.

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The mechanism of activation of the actin binding protein EHBP1 by Rab8 family members

Cited by 25 publications

References 46 publications

Actin-Associated Proteins and Small Molecules Targeting the Actin Cytoskeleton

Actin-Associated Proteins and Small Molecules Targeting the Actin Cytoskeleton

Spitz nevus with EHBP1‐ALK fusion and distinctive membranous localization of ALK

Genome-Wide Association Study of Alzheimer’s Disease Brain Imaging Biomarkers and Neuropsychological Phenotypes in the European Medical Information Framework for Alzheimer’s Disease Multimodal Biomarker Discovery Dataset

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