Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P41181 (
collecting duct
)
5,183
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Agrin, a multidomain proteoglycan and neurotrypsin, a neuronal serine protease, are important for forming (neuromuscular) synapses. Proteolytical activity of neurotrypsin produces a C-terminal fragment of agrin, termed
CAF
, of approximately 22 kDA molecular size which also circulates in blood. The presence of
CAF
in urine suggests either glomerular filtration or secretion into urine. Blood levels of
CAF
have been identified as a potential novel marker of kidney function. Here we describe that several nephron segments in the mouse kidney express agrin and neutrotrypsin in addition to the localization of both protein in the glomerulum. Agrin mRNA and protein was detected in almost all nephron segments and mRNA abundance was highest in the inner medullary
collecting duct
. Neurotrypsin mRNA was mostly detected in the thick ascending limb of the loop of Henle, the distal convoluted tubule, and the inner medullary
collecting duct
. Moreover, we show that the proximal tubule absorbs injected recombinant
CAF
by a process shared with receptor-mediated and fluid phase endocytosis. Co-injection of
CAF
with recombinant human transferrin, a substrate of the receptor-mediated endocytic pathway as well as with FITC-labelled dextran (10 kDa), a marker of fluid phase endocytosis, showed partial colocalization of
CAF
with both markers. Further colocalization of
CAF
with the lysosomal marker cathepsin B suggested degradation of
CAF
by the lysosome in the proximal tubule. Thus, the murine kidney expresses agrin and neurotrypsin in nephron segments beyond the glomerulum.
CAF
is filtered by the glomerulum and is reabsorbed by endocytosis by the proximal tubule. Thus, impaired kidney function could impair glomerular clearance of
CAF
and thereby increase circulating
CAF
levels.
...
PMID:The C-Terminal Fragment of Agrin (CAF), a Novel Marker of Renal Function, Is Filtered by the Kidney and Reabsorbed by the Proximal Tubule. 2738 Feb 75
