Neurexin-1, a presynaptic adhesion molecule, localizes at the slit diaphragm of the glomerular podocytes in kidneys.
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-1α were detected in the cerebrum, but only one form of neurexin-1α 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.
Dept. of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan.
Akira
A
Saito
Naoko
N
Miyauchi
Taeko
T
Hashimoto
Tamaki
T
Karasawa
Gi Dong
GD
Han
Mutsumi
M
Kayaba
Tomoyuki
T
Sumi
Masayuki
M
Tomita
Yohei
Y
Ikezumi
Kenji
K
Suzuki
Yasushi
Y
Koitabashi
Fujio
F
Shimizu
Hiroshi
H
Kawachi
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000595:Amino Acid Sequence; D000825:Animal Structures / Q000378:metabolism; D000818:Animals; D054022:Cerebrum / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics; D051528:Guanylate Kinases / Q000378:metabolism; D007678:Kidney Glomerulus / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics; D009479:Neuropeptides / Q000235:genetics; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics; D011507:Proteinuria / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D013047:Specific Pathogen-Free Organisms
D048868:Adaptor Proteins, Signal Transducing; C114545:CD2-associated protein; D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C547193:Nrxn1 protein, rat; D020033:Protein Isoforms; D011956:Receptors, Cell Surface; C113267:nephrin; C112162:neurexophilin; C086959:neurexin Ibeta; C106868:CASK kinases; D051528:Guanylate Kinases