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Acta Physiologica 2013; Volume 207, Supplement 694
92nd Annual Meeting of the German Physiological Society
3/2/2013-3/5/2013
Heidelberg, Germany
LOCALIZATION OF AGRIN AND NEUROTRYPSIN IN KIDNEY AND EXCRETION OF THE C-TERMINAL AGRIN FRAGMENT INTO URINE
Abstract number: P095
Daryadel
1
*A.
, Haubitz
2
M., Hettwer
2
S., Roos
3
M., Heemann
3
U., Vrijbloed
2
J.W., Wagner
1
C.A.
1
Institute of Physiology, Zurich, Switzerland
2
Neurotune AG , Schlieren, Switzerland
3
Klinikum rechts der Isar, Division of Nephrology, Munich, Germany
Agrin, a multidomain proteoglycan and Neurotrypsin, a neuronal serine protease, are important for forming(neuromuscular)synapses. Both proteins have been reported to be expressed also in the mammalian kidney. However, their exact localization has not been investigated in detail. The presence of the C-terminal fragment of agrin(CAF, approx 22 kDa)cleaved by neurotrypsin, in urine suggests either glomerular filtration or secretion into urine. RT-qPCR was performed on hand-dissected mouse nephrons and demonstrated agrin mRNA in the glomerulum and most segments but with highest expression in the late collecting duct(IMCD). Similarly, neurotrypsin mRNA was highest in the IMCD segment. In mouse kidney, agrin protein was detected in the basement membranes of the glomerulum and along all nephron segments. Neurotrypsin immunoreactivity was detected mostly in the apical region of the proximal tubule and with some lesser intensity in the basement membrane of the medullary collecting ducts. Staining for CAF was found both colocalizing with agrin as well as in the apical and subapcial region of the proximal tubule. No CAF was detected in kidneys from neurotrypsin(NT)KO mice. Systemic injection of recombinant human CAF into NT KO mice resulted in urinary excretion of intact CAF as well as its detection in endocytic vesicles in the proximal tubule. Thus, urinary CAF may at least in part originate from glomerular filtration. Increased levels of urinary CAF in patients with kidney disease may indicate both glomerular and proximal tubular damage.
To cite this abstract, please use the following information:
Acta Physiologica 2013; Volume 207, Supplement 694 :P095