LRRC26 Membrane Protein Introduction

Introduction of LRRC26

LRRC26, Leucine-rich repeat-containing protein 26 is a protein that in humans is encoded by the LRRC26 gene. The expression is found in prostate, colon, salivary gland. This gene is conserved in chimpanzee, rhesus monkey, dog, cow, mouse, rat and chicken. 139 organisms have orthologs with human gene LRRC26. The LRRs-domain of this protein participates in protein-protein interactions and has different functions and cellular locations.

Function of LRRC26 Membrane Protein

LRRC26 (Leucine-rich repeat-containing protein 26) is a transmembrane protein with only 1 transmembrane domain. It’s also known as CAPC. It’s a helper protein of the large-conductance, voltage and calcium-activated potassium channel (BK alpha). BK channels are composed of the homotetrameric pore-forming voltage, calcium-sensing α subunits (BKα), or associated with regulatory tissue-specific auxiliary β or γ subunits. BK channel auxiliary γ (BKγ) subunits are a group with leucine-rich repeat (LRR) domains, including γ1 (LRRC26), γ2 (LRRC52), γ3 (LRRC55), and γ4 (LRRC38). LRRC26 can modulate the gating characteristics by producing a marked shift in hyperpolarizing direction and in the absence of calcium. These subunits display distinct expression levels in different human tissues. LRRC26 is mainly expressed in secretory glands. Also, in non-excitable cells, it’s required for conversion of BK alpha channels with the state from a high-voltage to a low-voltage activated channel type. In addition, LRRC26 plays a role in myoblast differentiation, and in malignant progression of triple-negative breast cancer. Furthermore, it plays a critical role in supporting normal secretory function in all secretory epithelial cells via BK channels.

Fig.1 Structural features of LRRC26 (Yan, 2012)

Application of LRRC26 Membrane Protein in Literature

1. Ding J., et al. A transcriptomics study of differentiated C2C12 myoblasts identified novel functional responses to 17β-estradiol. Cell Biol Int. 2018, 42(8):965-974. PubMed ID: 29570902
   
   

   This article shows that LRRC26 is associated with the effects of E2 on myoblast differentiation.

2. Miyagawa Y., et al. Frequent downregulation of LRRC26 by epigenetic alterations is involved in the malignant progression of triple-negative breast cancer. Int J Oncol. 2018. PubMed ID: 29512727
   
   

   This article demonstrates that LRRC26 plays a critical role in the malignant progression of triple-negative breast cancer. LRRC26 deficiency can cause aggressiveness of TNBC cells via a TNF-α/NF-κB-independent mechanism.

3. Yang C., et al. Knockout of the LRRC26 subunit reveals a primary role of LRRC26-containing BK channels in secretory epithelial cells. Proc Natl Acad Sci U S A. 2017, 114(18):E3739-E3747. PubMed ID: 29662192
   
   

   This article indicates that LRRC26-containing BK channels are able to contribute to resting K⁺ efflux at normal cell membrane potentials with resting cytosolic calcium concentrations. It plays a critical role in supporting normal secretory function in all secretory epithelial cells.

4. Zhang J and Yan J. Regulation of BK channels by auxiliary γ subunits. Front Physiol. 2014, 5:401. PubMed ID: 25360119
   
   

   This article shows that LRRC26 can interact with BK channels to modulate the function. In non-excitable cells, it allows BK channels to keep an open status even at near physiological Ca²⁺ concentration and membrane voltage.

5. Evanson K.W., et al. LRRC26 is a functional BK channel auxiliary γ subunit in arterial smooth muscle cells. Circ Res. 2014, 115(4):423-31. PubMed ID: 24906643
   
   

   This article indicates that functional LRRC26 is expressed in arterial myocytes. And it can enhance channel voltage and apparent calcium sensitivity to induce vasodilation.

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Reference

1. Yan J and Aldrich R W. (2012). BK potassium channel modulation by leucine-rich repeat-containing proteins. Proc Natl Acad Sci U S A. 109(20):7917-22.

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