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The pallid gene encodes a novel, syntaxin 13-interacting protein involved in platelet storage pool deficiency

Nature Genetics volume 23, pages 329–332 (1999)Cite this article

Abstract

Pallid (pa) is 1 of 13 platelet storage pool deficiency (SPD) mouse mutants1,2,3. pa animals suffer from prolonged bleeding time, pigment dilution, kidney lysosomal enzyme elevation, serum α1-antitrypsin activity deficiency and abnormal otolith formation2,4,5,6. As with other mouse mutants of this class, characterization of pa mice suggests a defect in organelle biosynthesis. Here we describe the physical mapping, positional cloning, and mutational and functional analysis of the gene that is defective in pa mice. It encodes a ubiquitously expressed, highly charged 172–amino-acid protein (termed pallidin) with no homology to known proteins. We detected a nonsense mutation at codon 69 of this gene in the pallid mutant. In a yeast two-hybrid screen, we discovered that pallidin interacts with syntaxin 13, a t-SNARE protein that mediates vesicle-docking and fusion7,8. We confirmed this interaction by co-immunoprecipitation assay. Immunofluorescence studies corroborate that the cellular distribution of pallidin overlaps that of syntaxin 13. Whereas the mocha and pearl SPD mutants have defects in Ap-3 (Refs 9,10), our findings suggest that pa SPD mutants are defective in a more downstream event of vesicle-trafficking: namely, vesicle-docking and fusion.

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Figure 1: Genetic and physical maps of the pa region on mouse chromosome 2.
Figure 2: Expression of pa mRNA in tissues derived from C57BL/6J and pa animals.
Figure 3: Mouse pa cDNA (ORF) and predicted amino acid sequences (C57BL/6J).
Figure 4: Absence of pallidin in pa animals.
Figure 5: Biochemical and histological evidence for interaction of pallidin with syntaxin 13.

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Acknowledgements

We thank D. Ma, L. Pawlikowska, M.-C. Cheung, M. Gunthorpe, J. DeYoung and H. Consengco for technical assistance, advice and reagents, and members of our laboratory for discussions. Part of this research was supported by a grant from the NIDDK. J.G. is an investigator with the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Howard Hughes Medical Institute and Department of Medicine and Pediatrics, University of California, San Francisco, 94143-0794, California, USA

    Liping Huang & Jane Gitschier

  2. Department of Pediatrics, University of California, San Francisco, 94143-0794, California, USA

    Liping Huang & Jane Gitschier

  3. Pediatrics, University of California,, San Francisco, 94143-0794, California, USA

    Yien-Ming Kuo & Jane Gitschier

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  1. Liping Huang
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Correspondence to Jane Gitschier.

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Huang, L., Kuo, YM. & Gitschier, J. The pallid gene encodes a novel, syntaxin 13-interacting protein involved in platelet storage pool deficiency. Nat Genet 23, 329–332 (1999). https://doi.org/10.1038/15507

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