Tissue distribution and functional analysis of Sushi domain-containing protein 4.

Abstract	Sushi domain-containing protein 4 (SUSD4) was a hypothetical cell surface protein whose tissue distribution and function were completely unknown. However, recent microarray-based studies have identified deletions of SUSD4 gene in patients with autism or Fryns syndrome, both of which are genetic diseases with severe abnormal neurological development and/or functions. In this article, we described the cloning, expression, refolding, tissue distribution, and functional analysis of this novel protein. Using polyclonal antibodies generated by immunizing chickens with the recombinant SUSD4, we found that SUSD4 is detectable in murine brains, eyes, spinal cords, and testis but not other tissues. In brains, SUSD4 is highly expressed in the white matter on oligodendrocytes/axons, and in eyes, it is exclusively expressed on the photoreceptor outer segments. In in vitro complement assays, SUSD4 augments the alternative but not the classical pathway of complement activation at the C3 convertase step. In in vivo studies, knocking down SUSD4 expression in zebrafish markedly increases ratios of mortality and developmental abnormality. These results provide the first insight into the important physiological roles of SUSD4 and could help to better understand the pathogenesis of autism and Fryns syndrome.
Authors	Zhidan Tu, Mark Cohen, Hong Bu, Feng Lin
Journal	The American journal of pathology (Am J Pathol) Vol. 176 Issue 5 Pg. 2378-84 (May 2010) ISSN: 1525-2191 [Electronic] United States
PMID	20348246 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Complement C3 Complement Inactivator Proteins Membrane Proteins Protein Isoforms Recombinant Proteins sushi domain-containing protein 4, mouse
Topics	Animals Autistic Disorder (metabolism) Cell Membrane (metabolism) Complement C3 (chemistry) Complement Inactivator Proteins Disease Models, Animal Enzyme-Linked Immunosorbent Assay Facies Gene Deletion Hernia, Diaphragmatic (metabolism) Hernias, Diaphragmatic, Congenital Humans Limb Deformities, Congenital (metabolism) Membrane Proteins (chemistry, metabolism) Mice Mice, Inbred C57BL Models, Biological Protein Isoforms Recombinant Proteins (chemistry) Zebrafish

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