CRIM1 is localized to the podocyte filtration slit diaphragm of the adult human kidney.
BACKGROUND
CRIM1 is a plasma membrane bound protein containing six cysteine-rich repeats (CRR). Through these, CRIM1 has been shown to interact with a subgroup of the TGF-beta superfamily, the bone morphogenic proteins (BMP) isoforms 2, 4 and 7. The probable action is to modulate the signalling properties of these factors. CRIM1 has also been shown to regulate the release of VEGFA by podocytes during renal organogenesis. Knock-out studies in mice have shown that CRIM1 is critically involved in the development of the central nervous system, eye and kidney. Replacement of CRIM1 with a defective version leads to renal dysgenesis and perinatal death. We have analysed the distribution of CRIM1 in adult human renal tissue.


METHODS
To this end, we have used immunofluorescence, immunohistochemistry and immunoelectron microscopy. We performed western blotting for the CRIM1 protein, using lysates from isolated glomerular podocytes and human renal tissue homogenate. By using quantitative PCR, we compared the CRIM1 mRNA levels in podocytes, human renal tissue homogenate, primary human renal proximal tubular epithelial cells and primary human pulmonary artery smooth muscle cells.


RESULTS
The results show that in the human adult kidney, CRIM1 is mainly expressed in the glomerular podocytes and is associated with the insertional region of the filtration slit diaphragm (SD) of the podocyte pedicles.


CONCLUSIONS
CRIM1 is a protein that should be added to the list of proteins associated with the podocyte filtration SD and with the probable action of modulating BMP and VEGFA signalling.
Nyström
Jenny
J
Department of Nephrology, Göteborg University, Gothenburg, Sweden.
Hultenby
Kjell
K
Ek
Sara
S
Sjölund
Jonas
J
Axelson
Håkan
H
Jirström
Karin
K
Saleem
Moin A
MA
Nilsson
Kristina
K
Johansson
Martin E
ME
D000328:Adult; D052004:Bone Morphogenetic Protein Receptors; D002478:Cells, Cultured; D006801:Humans; D007668:Kidney / Q000737:chemistry*; D008565:Membrane Proteins / Q000032:analysis*; D050199:Podocytes / Q000737:chemistry*
C486175:CRIM1 protein, human; D008565:Membrane Proteins; D052004:Bone Morphogenetic Protein Receptors