Neurexin-1, a presynaptic adhesion molecule, localizes at the slit diaphragm of the glomerular podocytes in kidneys

Title
Neurexin-1, a presynaptic adhesion molecule, localizes at the slit diaphragm of the glomerular podocytes in kidneys
Author(s)
한기동사이토아키라[사이토아키라]미야우치 나오코[미야우치 나오코]하시모토 타헤코[하시모토 타헤코]카라사와 타마키[카라사와 타마키]카야바 무츠미[카야바 무츠미]수미 토모유키[수미 토모유키]토미타 마사유키[토미타 마사유키]이케주미 요헤이[이케주미 요헤이]스즈키 켄지[스즈키 켄지]코이타바시 야스시[코이타바시 야스시]시미즈 후지오[시미즈 후지오]카와치 히로시[카와치 히로시]
Keywords
FOCAL SEGMENTAL GLOMERULOSCLEROSIS; CONGENITAL NEPHROTIC SYNDROME; CELL-SURFACE PROTEINS; BETA-NEUREXINS; JUNCTION PROTEINS; ADHERENS JUNCTION; RAT NEPHRIN; EXPRESSION; PODOCIN; DOMAIN
Issue Date
201102
Publisher
AMER PHYSIOLOGICAL SOC
Citation
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, v.300, no.2, pp.R340 - R348
Abstract
Saito A, Miyauchi N, Hashimoto T, Karasawa T, Han GD, Kayaba M, Sumi T, Tomita M, Ikezumi Y, Suzuki K, Koitabashi Y, Shimizu F, Kawachi H. Neurexin-1, a presynaptic adhesion molecule, localizes at the slit diaphragm of the glomerular podocytes in kidneys. Am J Physiol Regul Integr Comp Physiol 300: R340-R348, 2011. First published November 3, 2010; doi: 10.1152/ajpregu.00640.2009.-The slit diaphragm connecting the adjacent foot processes of glomerular epithelial cells (podocytes) is the final barrier of the glomerular capillary wall and serves to prevent proteinuria. Podocytes are understood to be terminally differentiated cells and share some common features with neurons. Neurexin is a presynaptic adhesion molecule that plays a role in synaptic differentiation. Although neurexin has been understood to be specifically expressed in neuronal tissues, we found that neurexin was expressed in several organs. Several forms of splice variants of neurexin-1 alpha were detected in the cerebrum, but only one form of neurexin-1 alpha was detected in glomeruli. Immunohistochemical study showed that neurexin restrictedly expressed in the podocytes in kidneys. Dual-labeling analyses showed that neurexin was colocalized with CD2AP, an intracellular component of the slit diaphragm. Immunoprecipitation assay using glomerular lysate showed that neurexin interacted with CD2AP and CASK. These observations indicated that neurexin localized at the slit diaphragm area. The staining intensity of neurexin in podocytes was clearly lowered, and their staining pattern shifted to a more discontinuous patchy pattern in the disease models showing severe proteinuria. The expression and localization of neurexin in these models altered more clearly and rapidly than that of other slit diaphragm components. We propose that neurexin is available as an early diagnostic marker to detect podocyte injury. Neurexin coincided with nephrin, a key molecule of the slit diaphragm detected in a presumptive podocyte of the developing glomeruli and in the glomeruli for which the slit diaphragm is repairing injury. These observations suggest that neurexin is involved in the formation of the slit diaphragm and the maintenance of its function.
URI
http://hdl.handle.net/YU.REPOSITORY/25654http://dx.doi.org/10.1152/ajpregu.00640.2009
ISSN
0363-6119
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자연자원대학 > 식품공학과 > Articles
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