Yosuke Funato

IRSp53 has been characterized as an adaptor protein that links Rho-family small GTPases, such as Rac, to reorganization of the actin cytoskeleton. Here, we search for other binding partners for the IRSp53 SH3 domain and identify Eps8 as the major binding protein in fibroblasts and various cancer cell lines. Eps8 has been shown to form a Rac-specific guanine nucleotide exchange factor complex with Abi-1 and Sos-1, which seems essential for ruffling formation induced by oncogenic Ras. We confirm t

Intracellular Mg(2+) levels are strictly regulated; however, the biological importance of intracellular Mg(2+) levels and the pathways that regulate them remain poorly understood. Here, we determined that intracellular Mg(2+) is important in regulating both energy metabolism and tumor progression. We determined that CNNM4, a membrane protein that stimulates Mg(2+) efflux, binds phosphatase of regenerating liver (PRL), which is frequently overexpressed in malignant human cancers. Biochemical anal

Thioredoxin (TRX) family proteins are involved in various biologic processes by regulating the response to oxidative stress. Nucleoredoxin (NRX), a relatively uncharacterized member of the TRX family protein, has recently been reported to regulate the Wnt/beta-catenin pathway, which itself regulates cell fate and early development, in a redox-dependent manner. In this review, we describe the TRX family proteins and discuss in detail the similarities and differences between NRX and other TRX fami

The CNNM/CorC family proteins are Mg²⁺ transporters that are widely distributed in all domains of life. In bacteria, CorC has been implicated in the survival of pathogenic microorganisms. In humans, CNNM proteins are involved in various biological events, such as body absorption/reabsorption of Mg²⁺ and genetic disorders. Here, we determined the crystal structure of the Mg²⁺-bound CorC TM domain dimer. Each protomer has a single Mg²⁺ binding site with

Analyses of mice lacking CNNM Mg transporters clearly demonstrated abnormalities in BP values, confirming the importance of magnesium homeostasis in maintaining BP.

Cyclin M (CNNM) family proteins are evolutionarily conserved Mg2+ transporters. They extrude Mg2+ from cells and maintain intracellular Mg2+ levels within the normal range. Moreover, they play an important role in Mg2+ (re)absorption in the intestine and kidney by mediating the directional transport of Mg2+ across epithelial tissue from the tubular lumen to the body inside. Mg2+ efflux is suppressed by the direct binding with phosphatase of regenerating liver (PRL), and the formation of the comp

Magnesium (Mg) homeostasis is maintained by both intestinal absorption and renal reabsorption. Commonly, in these processes, Mg2+ is transported from the tubular lumen to the body interior, passing through epithelial sheets. Transcellular Mg2+ transport, which consists of Mg2+ influx at the apical membrane and Mg2+ efflux at the basolateral membrane, plays important roles in transepithelial Mg2+ (re)absorption. Mg2+-permeable cation channels TRPM6 and TRPM7 mediate apical Mg2+ influx (Schlingman

The Wnt signaling pathway is conserved across species, and is essential for early development. We previously identified nucleoredoxin (NRX) as a protein that interacts with dishevelled (Dvl) in vivo to negatively regulate the Wnt/beta-catenin pathway. However, whether NRX affects another branch of the Wnt pathway, the Wnt/planar cell polarity (PCP) pathway, remains unclear. Here we show that NRX regulates the Wnt/PCP pathway. In Xenopus laevis, over-expression or depletion of NRX by injection of

<b><i>Aims:</i></b> Mg²⁺ is fundamental for life, and its shortage severely impairs vital functions. However, whether excessive Mg²⁺ has beneficial or adverse effects has remained unknown. To clarify this issue, we analyzed the effect of suppressing the functions of Cyclin M (CNNM) Mg²⁺ efflux transporters in various experimental systems. <b><i>Results:</i></b> Investigation of short-lived <i>Caenorhabditis elegans</i> worms mutated for CNNM genes revealed reacti

Mg2+ serves as an essential cofactor for numerous enzymes and its levels are tightly regulated by various Mg2+ transporters. Here, we analyzed Caenorhabditis elegans strains carrying mutations in genes encoding cyclin M (CNNM) Mg2+ transporters. We isolated inactivating mutants for each of the five Caenorhabditis elegans cnnm family genes, cnnm-1 through cnnm-5. cnnm-1; cnnm-3 double mutant worms showed various phenotypes, among which the sterile phenotype was rescued by supplementing the media

Blood pressure has a daily pattern, with higher values in the active period. Its elevation at the onset of the active period substantially increases the risk of fatal cardiovascular events. Renin secretion stimulated by renal sympathetic neurons is considered essential to this process; however, its regulatory mechanism remains largely unknown. Here, we show the importance of transient receptor potential melastatin-related 6 (TRPM6), a Mg²⁺-permeable cation channel, in augmenting renin