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| Identification of the homologous beige and Chediak-Higashi syndrome genes |
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| Author(s): Barbosa MDFS, Nguyen QA, Tchernev VT, Ashley JA, Detter JC, Blaydes SM, Brandt SJ, Chotai D, Hodgman C, Solari RCE, Lovett M, Kingsmore SF |
| Source: NATURE Volume: 382 Issue: 6588 Pages: 262-265 Published: JUL 18 1996 |
| Times Cited: 245 References: 30 |
| Abstract: VESICULAR transport to and from the lysosome and late endosome is defective in patients with Chediak-Higashi syndrome (CHS) and in mutant beige (bg) mice(1-4). CHS and bg cells have giant, perinuclear vesicles with characteriscs of late endosomes and lysosomes that arise from dysregulated homotypic fusion(3-5). CHS and bg lysosomes also exhibit compartmental missorting of proteins, such as elastase, glucuronidase and cathepsin G(2,3,6,7) Lyst, a candidate gene for bg, was identified by direct complementary DNA selection from a yeast artificial chromosome (YAC) clone containing a 650-kilobase segment of the bg-critical region on mouse chromosome 13. Lyst is disrupted by a 5-kilobase deletion in bg(11J) mice, and Lyst messenger RNA is markedly reduced in bg(2J) homozygotes. The homologous human gene, LYST, is highly conserved with mouse Lyst, and contains a frame-shift mutation at nucleotides 117-118 of the coding domain in a CHS patient. Thus bg mice and human CHS patients have homologous disorders associated with Lyst mutations. Lyst encodes a protein with a carboxy-terminal prenylation motif and multiple potential phosphorylation sites. Lyst protein is predicted to form extended helical domains, and has a region of sequence similar to stathmin, a coiled coil phosphoprotein thought to act as a relay integrating cellular signal response coupling(8-10). |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV FLORIDA, DEPT MED, GAINESVILLE, FL 32610 USA
2. UNIV FLORIDA, DEPT PATHOL, GAINESVILLE, FL 32610 USA
3. UNIV FLORIDA, CTR MAMMALIAN GENET, GAINESVILLE, FL 32610 USA
4. UNIV TEXAS, SW MED CTR, DEPT BIOCHEM, DALLAS, TX 75235 USA
5. UNIV TEXAS, SW MED CTR, MCDERMOTT CTR, DALLAS, TX 75235 USA
6. VANDERBILT UNIV, DEPT MED, NASHVILLE, TN 37232 USA
7. VANDERBILT UNIV, DEPT CELL BIOL, NASHVILLE, TN 37232 USA
8. GLAXO WELLCOME MED RES CTR, CELL BIOL UNIT, STEVENAGE SG1 2NY, HERTS ENGLAND
9. GLAXO WELLCOME MED RES CTR, ADV TECHNOL UNIT, STEVENAGE SG1 2NY, HERTS ENGLAND
10. GLAXO WELLCOME MED RES CTR, INFORMAT UNIT, STEVENAGE SG1 2NY, HERTS ENGLAND |
| Publisher: MACMILLAN MAGAZINES LTD, 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: UX790 |
| ISSN: 0028-0836 |
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