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PMID: 10859366 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

A mutation in Rab27a causes the vesicle transport defects observed in ashen mice.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 97 ·No. 14 ·2000-07-05 ·Pages 7933-8

Wilson SM, Yip R, Swing DA, O'Sullivan TN, Zhang Y, Novak EK, Swank RT, Russell LB, Copeland NG, Jenkins NA

Abstract

The dilute (d), leaden (ln), and ashen (ash) mutations provide a unique model system for studying vesicle transport in mammals. All three mutations produce a lightened coat color because of defects in pigment granule transport. In addition, all three mutations are suppressed by the semidominant dilute-suppressor (dsu), providing genetic evidence that these mutations function in the same or overlapping transport pathways. Previous studies showed that d encodes a major vesicle transport motor, myosin-VA, which is mutated in Griscelli syndrome patients. Here, using positional cloning and bacterial artificial chromosome rescue, we show that ash encodes Rab27a. Rab GTPases represent the largest branch of the p21 Ras superfamily and are recognized as key players in vesicular transport and organelle dynamics in eukaryotic cells. We also show that ash mice have platelet defects resulting in increased bleeding times and a reduction in the number of platelet dense granules. These defects have not been reported for d and ln mice. Collectively, our studies identify Rab27a as a critical gene for organelle-specific protein trafficking in melanocytes and platelets and suggest that Rab27a functions in both MyoVa dependent and independent pathways.

MeSH Terms
Albinism, Oculocutaneous Animals Biological Transport/genetics Blood Platelets/pathology Chromosome Mapping Cytoplasmic Granules/parasitology Disease Models, Animal Gene Library Genetic Complementation Test Hair Color/genetics Intermediate Filament Proteins/metabolism Intracellular Membranes/metabolism Melanocytes/metabolism,ultrastructure Mice Mice, Inbred C3H Mice, Mutant Strains Muridae Myosin Heavy Chains Myosin Type V Protein Binding RNA Splicing Skin/cytology Syndrome rab GTP-Binding Proteins/genetics rab27 GTP-Binding Proteins
Chemicals
Intermediate Filament Proteins Myo5a protein, mouse rab27 GTP-Binding Proteins Myosin Type V Rab27a protein, mouse Myosin Heavy Chains rab GTP-Binding Proteins
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Wilson S M
Mouse Cancer Genetics Program, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702, USA.
Yip R
Swing D A
O'Sullivan T N
Zhang Y
Novak E K
Swank R T
Russell L B
Copeland N G
Jenkins N A
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.140212797
Published
2000-07-05
Pages
7933-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC16648
Subset
IM
Grants
NCI NIH HHS · P30 CA016056 · United States
NCI NIH HHS · CA16056 · United States
NHLBI NIH HHS · R01 HL031698 · United States
NEI NIH HHS · EY12104 · United States
NEI NIH HHS · R01 EY012104 · United States
NHLBI NIH HHS · HL31698 · United States
External Links
PubMed source DOI: 10.1073/pnas.140212797 PMC Full Text View journal details
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