CRIM1 explained

Cysteine-rich motor neuron 1 protein is a protein that in humans is encoded by the CRIM1 gene.^{[1] [2]}

Function

Motor neurons are among the earliest neurons to appear after the commencement of cell patterning and the beginning of cell differentiation. Differentiation occurs in a ventral-to-dorsal gradient and is mediated, at least in part, by the concentration of ventrally expressed sonic hedgehog protein (SHH; MIM 600725). Dorsally expressed factors, such as members of the bone morphogenic protein (e.g., BMP4; MIM 112262) and transforming growth factor-beta (e.g., TGFB1; MIM 190180) families, can repress the induction of these neurons. CRIM1 may interact with growth factors implicated in motor neuron differentiation and survival.^[1]

Clinical significance

Loss of Crim1 function as demonstrated by the Crim1 KST264 hypomorph mice resulted in onset of chronic kidney disease with accompanying pathology including papillary hypoplasia, functional urinary tract obstruction, ectopic collagen accumulation within the endothelium and tubulointerstitial fibrosis which was in part attributed by (endothelial) epithelial–mesenchymal transition.^{[3] [4]}

Further reading

• Wilkinson L, Kurniawan ND, Phua YL, Nguyen MJ, Li J, Galloway GJ, Hashitani H, Lang RJ, Little MH . Association between congenital defects in papillary outgrowth and functional obstruction in Crim1 mutant mice . The Journal of Pathology . 227 . 4 . 499–510 . Aug 2012 . 22488641 . 10.1002/path.4036 . 2777257 .
• Phua YL, Martel N, Pennisi DJ, Little MH, Wilkinson L . Distinct sites of renal fibrosis in Crim1 mutant mice arise from multiple cellular origins . The Journal of Pathology . 229 . 5 . 685–96 . Apr 2013 . 23224993 . 10.1002/path.4155 . 22837861 .
• Pennisi DJ, Wilkinson L, Kolle G, Sohaskey ML, Gillinder K, Piper MJ, McAvoy JW, Lovicu FJ, Little MH . Crim1KST264/KST264 mice display a disruption of the Crim1 gene resulting in perinatal lethality with defects in multiple organ systems . Developmental Dynamics . 236 . 2 . 502–11 . Feb 2007 . 17106887 . 10.1002/dvdy.21015 . 1563138 . free .
• Zhang Z, Henzel WJ . Signal peptide prediction based on analysis of experimentally verified cleavage sites . Protein Science . 13 . 10 . 2819–24 . Oct 2004 . 15340161 . 2286551 . 10.1110/ps.04682504 .
• Wilkinson L, Kolle G, Wen D, Piper M, Scott J, Little M . CRIM1 regulates the rate of processing and delivery of bone morphogenetic proteins to the cell surface . The Journal of Biological Chemistry . 278 . 36 . 34181–8 . Sep 2003 . 12805376 . 10.1074/jbc.M301247200 . free .
• Glienke J, Sturz A, Menrad A, Thierauch KH . CRIM1 is involved in endothelial cell capillary formation in vitro and is expressed in blood vessels in vivo . Mechanisms of Development . 119 . 2 . 165–75 . Dec 2002 . 12464430 . 10.1016/S0925-4773(02)00355-6 . 7308653 . free .
• Georgas K, Bowles J, Yamada T, Koopman P, Little MH . Characterisation of Crim1 expression in the developing mouse urogenital tract reveals a sexually dimorphic gonadal expression pattern . Developmental Dynamics . 219 . 4 . 582–7 . Dec 2000 . 11084657 . 10.1002/1097-0177(2000)9999:9999<::AID-DVDY1072>3.0.CO;2-I . free .

Notes and References

1. Kolle G, Georgas K, Holmes GP, Little MH, Yamada T . CRIM1, a novel gene encoding a cysteine-rich repeat protein, is developmentally regulated and implicated in vertebrate CNS development and organogenesis . Mechanisms of Development . 90 . 2 . 181–93 . Feb 2000 . 10642437 . 10.1016/S0925-4773(99)00248-8 . 6529349 . free .
2. Web site: Entrez Gene: CRIM1 cysteine rich transmembrane BMP regulator 1 (chordin-like).
3. Phua YL, Martel N, Pennisi DJ, Little MH, Wilkinson L . Distinct sites of renal fibrosis in Crim1 mutant mice arise from multiple cellular origins . The Journal of Pathology . 229 . 5 . 685–96 . Apr 2013 . 23224993 . 10.1002/path.4155 . 22837861 .
4. Wilkinson L, Kurniawan ND, Phua YL, Nguyen MJ, Li J, Galloway GJ, Hashitani H, Lang RJ, Little MH . Association between congenital defects in papillary outgrowth and functional obstruction in Crim1 mutant mice . The Journal of Pathology . 227 . 4 . 499–510 . Aug 2012 . 22488641 . 10.1002/path.4036 . 2777257 .