New Functions of Vav Family Proteins in Cardiovascular Biology, Skeletal Muscle, and the Nervous System

Abstract

Vav proteins act as tyrosine phosphorylation-regulated guanosine nucleotide exchange factors for Rho GTPases and as molecular scaffolds. In mammals, this family of signaling proteins is composed of three members (Vav1, Vav2, Vav3) that work downstream of protein tyrosine kinases in a wide variety of cellular processes. Recent work with genetically modified mouse models has revealed that these proteins play key signaling roles in vascular smooth and skeletal muscle cells, specific neuronal subtypes, and glia cells. These functions, in turn, ensure the proper regulation of blood pressure levels, skeletal muscle mass, axonal wiring, and fiber myelination events as well as systemic metabolic balance. The study of these mice has also led to the discovery of new physiological interconnection among tissues that contribute to the ontogeny and progression of different pathologies such as, for example, hypertension, cardiovascular disease, and metabolic syndrome. Here, we provide an integrated view of all these new Vav family-dependent signaling and physiological functions.

Rho GTPases in Skeletal Muscle Development and Homeostasis

“…By contrast, mice expressing a catalytically hyperactive version of Vav2 show increased muscle mass and resistance against all the foregoing metabolic dysfunctions even when fed with a high-fat diet [ 46 ]. A detailed description of the role of Vav2 in skeletal muscle and associated metabolic process can be found in a recent review [ 32 ]. In line with this, several clinical studies have established links between reductions in lean mass and type II diabetes [ 111 , 113 ].…”

“…Their roles in the regulation of physiological and pathological processes are equally wide. For example, it is known that Rho GTPases coordinate the differentiation of several cell types and that they play crucial roles in the regulation of immunological responses, blood pressure levels, and glucose homeostasis [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. As a result, alterations in their activity due to mutations, changes in expression and the deregulation of upstream and downstream signals can lead to a number of diseases such as cancer or cardiovascular, neurological, autoimmune, and immunodeficiency disorders [ 28 , 33 , 34 ].…”

“…In this review, we will address their intrinsic roles in those processes that have been discovered during these last years. Prior reviews on some of these aspects can be found elsewhere [ 10 , 24 , 26 , 32 , 35 , 36 ].…”

A rigorous in silico genomic interrogation at 1p13.3 reveals 16 autosomal dominant candidate genes in syndromic neurodevelopmental disorders

“…In mice, knocking out the Vav3 gene produces broad physiological changes due to significant issues with sympathetic nervous system modulation (SNS). This is because Vav3 is involved in the formation of appropriate inhibitory GABAergic circuitry between the caudal (CVLM) and rostral (RVLM) ventrolateral medullas in the brainstem (Sauzeau et al, 2010;Rodriguez-Fdez et al, 2021) 7. In the postnatal stage, Vav3 mice display significant motor coordination and gaiting impairments.…”

High Expression of VAV Gene Family Predicts Poor Prognosis of Acute Myeloid Leukemia

“…They are a group of signal transduction molecules regulated by tyrosine phosphorylation. 3 This gene family is related to the occurrence, development, and prognosis of many cancers. In non-small cell lung cancer, VAV2 is involved in the inhibition of the epithelial-mesenchymal transition, migration, and metastasis 4 and VAV3 can promote the metastasis.…”