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Drosophila GPI-mannosyltransferase 2 is required for GPI anchor attachment and surface expression of chaoptin

Published online by Cambridge University Press:  10 May 2012

ERICA E. ROSENBAUM ,
KIMBERLEY S. BREHM ,
EVA VASILJEVIC ,
ALLEN GAJESKI  and
NANSI JO COLLEY
ERICA E. ROSENBAUM
Affiliation:
Department of Ophthalmology & Visual Sciences, Department of Genetics, and The Eye Research Institute, University of Wisconsin, Madison, Wisconsin Neuroscience Training Program, University of Wisconsin, Madison, Wisconsin
KIMBERLEY S. BREHM
Affiliation:
Department of Ophthalmology & Visual Sciences, Department of Genetics, and The Eye Research Institute, University of Wisconsin, Madison, Wisconsin
EVA VASILJEVIC
Affiliation:
Department of Ophthalmology & Visual Sciences, Department of Genetics, and The Eye Research Institute, University of Wisconsin, Madison, Wisconsin
ALLEN GAJESKI
Affiliation:
Department of Ophthalmology & Visual Sciences, Department of Genetics, and The Eye Research Institute, University of Wisconsin, Madison, Wisconsin
NANSI JO COLLEY*
Affiliation:
Department of Ophthalmology & Visual Sciences, Department of Genetics, and The Eye Research Institute, University of Wisconsin, Madison, Wisconsin
*
*Address correspondence and reprint requests to: Dr. Nansi Jo Colley, Department of Ophthalmology & Visual Sciences, K6/460, 600 Highland Avenue, Madison, WI, 53792. E-mail: [email protected]
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Abstract

Glycosylphosphatidylinositol (GPI) anchors are critical for the membrane attachment of a wide variety of essential signaling and cell adhesion proteins. The GPI anchor is a complex glycolipid structure that utilizes glycosylphosphatidylinositol-mannosyltransferases (GPI-MTs) for the addition of three core mannose residues during its biosynthesis. Here, we demonstrate that Drosophila GPI-MT2 is required for the GPI-mediated membrane attachment of several GPI-anchored proteins, including the photoreceptor-specific cell adhesion molecule, chaoptin. Mutations in gpi-mt2 lead to defects in chaoptin trafficking to the plasma membrane in Drosophila photoreceptor cells. In gpi-mt2 mutants, loss of sufficient chaoptin in the membrane leads to microvillar instability, photoreceptor cell pathology, and retinal degeneration. Finally, using site-directed mutagenesis, we have identified key amino acids that are essential for GPI-MT2 function and cell viability in Drosophila. Our findings on GPI-MT2 provide a mechanistic link between GPI anchor biosynthesis and protein trafficking in Drosophila and shed light on a novel mechanism for inherited retinal degeneration.

Keywords

Drosophila photoreceptorProtein traffickingRetinal degenerationGPI anchor biosynthesisSecretory pathway
Type
Research Articles
Information
Visual Neuroscience , Volume 29 , Issue 3 , May 2012 , pp. 143 - 156
Copyright
Copyright © Cambridge University Press 2012

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