WASHC4

Last update 23 Jan 2025

Basic Info

Synonyms

KIAA1033, Strumpellin and WASH-interacting protein, SWIP

+ [3]

Introduction

Acts as a component of the WASH core complex that functions as a nucleation-promoting factor (NPF) at the surface of endosomes, where it recruits and activates the Arp2/3 complex to induce actin polymerization, playing a key role in the fission of tubules that serve as transport intermediates during endosome sorting.

100 Clinical Results associated with WASHC4

100 Translational Medicine associated with WASHC4

0 Patents (Medical) associated with WASHC4

Literatures (Medical) associated with WASHC4

01 May 2023·Traffic (Copenhagen, Denmark)

SWIP mediates retromer-independent membrane recruitment of the WASH complex.

Article

Author: Pacalt, Ondrej ; Berankova, Pavla ; Libusova, Lenka ; Dostal, Vojtech ; Humhalova, Tereza

The pentameric WASH complex facilitates endosomal protein sorting by activating Arp2/3, which in turn leads to the formation of F-actin patches specifically on the endosomal surface. It is generally accepted that WASH complex attaches to the endosomal membrane via the interaction of its subunit FAM21 with the retromer subunit VPS35. However, we observe the WASH complex and F-actin present on endosomes even in the absence of VPS35. We show that the WASH complex binds to the endosomal surface in both a retromer-dependent and a retromer-independent manner. The retromer-independent membrane anchor is directly mediated by the subunit SWIP. Furthermore, SWIP can interact with a number of phosphoinositide species. Of those, our data suggest that the interaction with phosphatidylinositol-3,5-bisphosphate (PI(3,5)P₂ ) is crucial to the endosomal binding of SWIP. Overall, this study reveals a new role of the WASH complex subunit SWIP and highlights the WASH complex as an independent, self-sufficient trafficking regulator.

01 Jul 2022·GeneQ3 · BIOLOGY

Genome-wide elucidation of CNV regions and their association with production and reproduction traits in composite Vrindavani cattle

Q3 · BIOLOGY

Article

Author: Singh, Akansha ; Malla, Waseem Akram ; Ahmad, Sheikh Firdous ; Dutt, Triveni ; Panda, Snehasmita ; Kumar, Amit

The present study was aimed to analyze the genome-wide copy number variations (CNVs) in Vrindavani composite cattle and concatenate them into CNV regions (CNVRs), and finally test the association of CNVRs with different production and reproduction traits. Genotypic data, generated on BovineSNP50 Beadchip (v3) array for 96 Vrindavani animals, was used to elucidate the CNVs at the genome level. Intensity data covering over 53,218 SNP genotypes on bovine genome was used. Algorithm based on Hidden Markov Model was employed in PennCNV program to detect, normalize and filter CNVs across the genome. 252 putative CNVs, detected via PennCNV program, in different individuals were concatenated into 71 CNV regions (CNVRs) using CNVRuler program. Association of CNVRs with important (re)production traits in Vrindavani animals was assessed using linear regression. Five CNVRs were found to be significantly associated with ten important (re)production traits. The genes harbored in these regions provided useful insights into the association of CNVRs with genes and ultimately the variation at phenotype level. Important genes that overlapped with CNVRs included WASHC4, HS6ST3, MBNL2, TOLLIP, PIDD1 and TSPAN4. Furthermore, the CNVRs were found to overlap with important QTLs available in AnimalQTL database which affect milk yield and composition along with reproduction and immune function traits. The copy number states of three enes were validated using digital droplet PCR technique. The results from the present study significantly enhance the understanding about CNVs in Vrindavani cattle and should help establish its CNV map. The study will also enable further investigation on association of these variants with important traits of economic interest including disease incidence.

01 Jan 2022·The Journal of PathologyQ1 · MEDICINE

Homozygous WASHC4 variant in two sisters causes a syndromic phenotype defined by dysmorphisms, intellectual disability, profound developmental disorder, and skeletal muscle involvement

Q1 · MEDICINE

Article

Author: Horvath, Rita ; Lochmüller, Hanns ; Christiansen, Jon ; Kaiser, Frank J. ; Münchberg, Ute ; Töpf, Ana ; Kölbel, Heike ; Sickmann, Albert ; Kiewert, Cordula ; Kuechler, Alma ; Hentschel, Andreas ; Schara‐Schmidt, Ulrike ; Roos, Andreas ; O'Heir, Emily ; Gangfuß, Andrea ; Czech, Artur ; Stehling, Florian

AbstractRecessive variants in WASHC4 are linked to intellectual disability complicated by poor language skills, short stature, and dysmorphic features. The protein encoded by WASHC4 is part of the Wiskott–Aldrich syndrome protein and SCAR homolog family, co‐localizes with actin in cells, and promotes Arp2/3‐dependent actin polymerization in vitro. Functional studies in a zebrafish model suggested that WASHC4 knockdown may also affect skeletal muscles by perturbing protein clearance. However, skeletal muscle involvement has not been reported so far in patients, and precise biochemical studies allowing a deeper understanding of the molecular etiology of the disease are still lacking. Here, we report two siblings with a homozygous WASHC4 variant expanding the clinical spectrum of the disease and provide a phenotypical comparison with cases reported in the literature. Proteomic profiling of fibroblasts of the WASHC4‐deficient patient revealed dysregulation of proteins relevant for the maintenance of the neuromuscular axis. Immunostaining on a muscle biopsy derived from the same patient confirmed dysregulation of proteins relevant for proper muscle function, thus highlighting an affliction of muscle cells upon loss of functional WASHC4. The results of histological and coherent anti‐Stokes Raman scattering microscopic studies support the concept of a functional role of the WASHC4 protein in humans by altering protein processing and clearance. The proteomic analysis confirmed key molecular players in vitro and highlighted, for the first time, the involvement of skeletal muscle in patients. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

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WASHC4

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