CNNM4

Last update 23 Jan 2025

Basic Info

Synonyms

ACDP4, Ancient conserved domain-containing protein 4, CNNM4

+ [4]

Introduction

Probable metal transporter. The interaction with the metal ion chaperone COX11 suggests that it may play a role in sensory neuron functions (By similarity). May play a role in biomineralization and retinal function.

100 Clinical Results associated with CNNM4

100 Translational Medicine associated with CNNM4

0 Patents (Medical) associated with CNNM4

103

Literatures (Medical) associated with CNNM4

01 Jan 2025·Structure

AI decodes CNNM Na+/Mg2+ exchange

Article

Author: Runnels, Loren W ; Nethramangalath, Thushara

In this issue of Structure, Ma et al.¹ apply the artificial intelligence system AlphaFold2, which was designed to predict three-dimensional protein structures from amino acid sequences with atomic accuracy, to model the conformal dynamics of the prokaryotic TpCorC and human CNNM2 and CNNM4 transporters, providing mechanistic insight into how sodium drives magnesium efflux.

31 Dec 2024·Preventive Nutrition and Food Science

Effects of Magnesium Forms on the Magnesium Balance and Jejunal Transporters in Healthy Rats

Article

Author: Er, Besir

Magnesium (Mg) is a mineral necessary for many biological activities in mammals. Here, we compared the effect of two Mg compounds [Mg picolinate (MgPic) to Mg oxide (MgO)] on Mg bioavailability and intestinal Mg and calcium transporter protein levels. Three groups of 21 male Wistar-Albino rats were randomly allocated and fed a standard diet (control) or a 500 mg/kg Mg-supplemented (MgPic or MgO) diet for 8 weeks. The serum and liver Mg levels, Mg absorptivity, and retentivity were augmented in the MgPic group compared with the MgO group (P<0.05). Only MgPic supplementation elevated the expression of the genes encoding CLDN2, CLDN15, CNNM4, NCX1, PMCA1b, NCX2, and Calbindin-D9k in the jejunum by 1.59, 1.58, 1.70, 1.82, 2.02, 2.03, and 2.31 fold, respectively (P<0.05). Compared to the MgO-fed rats, MgPic rats had higher expression of the genes encoding NCX1, NCX2, PMCA1b, and Calbindin-D9k in the jejunum by 1.43, 1.72, 1.54, and 1.69 fold, respectively (P<0.01). These results suggest that MgPic increases Mg absorptivity and retentivity more than Mg bioavailability. In addition, MgPic can improve the paracellular and transcellular cationic mineral transport process. Thus, Mg deficiency disorders might be alleviated by MgPic more effectively than MgO.

01 Dec 2024·Advanced Science

Thermogenic Adipocytes Promote M2 Macrophage Polarization through CNNM4‐Mediated Mg Secretion

Article

Author: Li, Huaming ; Luan, Bing ; Zhang, Chuan ; Shao, Anwen ; Lu, Zhangming ; Wang, Xiaoyu ; Fan, Haonan ; Zhang, Anke ; Zhang, Xiaonong ; Deng, Yuqing ; Jiang, Junkun ; Zhang, Zhen‐Ning ; Chen, Sheng ; Wang, Wenhui ; Yuan, Ling ; Ni, Jiahua ; Xu, Houshi ; Zhang, Jianmin ; Yu, Wenjing ; Fang, Chaoyou

AbstractM2 macrophages promote adipose tissue thermogenesis which dissipates energy in the form of heat to combat obesity. However, the regulation of M2 macrophages by thermogenic adipocytes is unclear. Here, it is identified magnesium (Mg) as a thermogenic adipocyte‐secreted factor to promote M2 macrophage polarization. Mg transporter Cyclin and CBS domain divalent metal cation transport mediator 4 (CNNM4) induced by ADRB3‐PKA‐CREB signaling in thermogenic adipocytes during cold exposure mediates Mg efflux and Mg in turn binds to the DFG motif in mTOR to facilitate mTORC2 activation and M2 polarization in macrophages. In obesity, downregulation of CNNM4 expression inhibits Mg secretion from thermogenic adipocytes, which leads to decreased M2 macrophage polarization and thermogenesis. As a result, CNNM4 overexpression in adipocytes or Mg supplementation in adipose tissue ameliorates obesity by promoting thermogenesis. Importantly, an Mg wire implantation (AMI) approach is introduced to achieve adipose tissue‐specific long‐term Mg supplement. AMI promotes M2 macrophage polarization and thermogenesis and ameliorates obesity in mice. Taken together, a reciprocal regulation of thermogenic adipocytes and M2 macrophages important for thermogenesis is identified, and AMI is offered as a promising strategy against obesity.

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CNNM4

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