Isolation of the gene for McLeod syndrome that encodes a novel membrane transport protein

doi:10.1016/0092-8674(94)90136-8

Cell

Volume 77, Issue 6, 17 June 1994, Pages 869-880

https://doi.org/10.1016/0092-8674(94)90136-8 Get rights and content

Abstract

McLeod syndrome is an X-linked multisystem disorder characterized by abnormalities in the neuromuscular and hematopoietic systems. We have assembled a cosmid contig of 360 kb that encompasses the McLeod gene locus. A 50 kb deletion was detected by screening DNA from patients with radiolabeled whole cosmids, and two transcription units were identified within this deletion. The mRNA expression pattern of one of them, designated as XK, correlates closely to the McLeod phenotype. XK encodes a novel protein with structural characteristics of prokaryotic and eukaryotic membrane transport proteins. Nucleotide sequence analysis of XK from two unrelated McLeod patients has identified point mutations at conserved splice donor and acceptor sites. These findings provide direct evidence that XK is responsible for McLeod syndrome.

References (76)

S.F. Altschul et al.
Basic local alignment search tool
J. Mol. Biol.
(1990)
J.L. Arriza et al.
Cloning and expression of a human neutral amino acid transporter with structural similarity to the glutamate transporter gene family
J. Biol. Chem.
(1993)
W.G. Cole et al.
A base substitution at a splice site in the COL3A1 gene causes exon skipping and generates abnormal type III procollagen in a patient with Ehlers-Danlos syndrome type IV
J. Biol. Chem.
(1990)
M. DiFiglia
Excitotoxic injury of the neostriatum: a model for Huntington's disease
Trends Neurosci
(1990)
A.P. Feinberg et al.
A technique for radiolabeling DNA restriction fragments to high specific activity
Biochem. Biophys. Res. Commun.
(1983)
B.E. Kemp et al.
Protein kinase recognition sequence motif
Trends Biochem. Sci.
(1990)
P.J. Kennelly et al.
Consensus sequences as substrate specificity determinants for protein kinases and protein phosphatases
J. Biol. Chem.
(1991)
K. Kirk et al.
Transport of diverse substrates into malaria-infected erythrocytes via a pathway showing functional characteristics of a chloride channel
J. Biol. Chem.
(1994)
J. Kyte et al.
A simple method for displaying the hydropathy character of a protein
J. Mol. Biol.
(1982)
F.A. Kuypers et al.
The phospholipid organization in the membranes of McLeod and Leach phenotype erythrocytes
FEBS Lett.
(1985)

S. Lee et al.

The human Kell blood group maps to chromosome 7q33 and its expression is restricted to erythroid cells

Blood

(1993)

C.M. Redman et al.

Kell blood group antigens are part of a 93,000 dalton red cell membrane protein

J. Biol. Chem.

(1986)

P. Senapathy et al.

Splice junctions, branch point sites, and exons: sequence statistics, identification, and applications to the genome project

Meth. Enzymol.

(1990)

S. Shafqat et al.

Cloning and expression of a novel Na⁺-dependent neutral amino acid transporter structurally related to mammalian $Na^{+} glutamate$ cotransporters

J. Biol. Chem.

(1993)

R. Treisman et al.

A single-base change at a splice site in a β⁰-thalassemic gene causes abnormal RNA splicing

Cell

(1982)

G.R. Uhl

Neurotransmitter transporters (plus): a promising new gene family

Trends Neurosci.

(1992)

G.R. Uhl et al.

Transporter explosion: update on uptake

Trends Pharmacol.

(1992)

D. Weil et al.

Identification of a mutation that causes exon skipping during collagen pre-mRNA splicing in an Ehlers-Danlos syndrome variant

J. Biol. Chem.

(1988)

S.G. Amara

Neurotransmitter transporters: recent progress

Annu. Rev. Neurosci.

(1993)

S. Baxendale et al.

The direct screening of cosmid libraries with yeast artificial chromosomes

Nucl. Acidś Res.

(1991)

C.J. Bertelson et al.

Localization of the McLeod locus (XK) within Xp21 by deletion analysis

Am. J. Hum. Genet.

(1988)

A.P. Bird

CpG-rich islands and the function of DNA methylation

Nature

(1986)

R.D. Blakely et al.

Cloning and expression of a functional serotonin transporter from rat brain

Nature

(1991)

W.G. Bradley et al.

Studies of sarcolemmal integrity in myopathic muscle

Neurology

(1978)

C.J. Brandl et al.

Hypothesis about the function of membrane-buried proline residues in transport proteins

R. Callender et al.

Resonance raman studies of visual pigments

Annu. Rev. Biophys. Bioeng.

(1977)

S. Carpenter et al.

Duchenne muscular dystrophy: plasma membrane loss initiates muscle cell necrosis unless it is repaired

Brain

(1979)

N.D. Carter et al.

Dystrophin expression and genotypic analysis of two cases of benign X-linked myopathy (McLeod's syndrome)

J. Med. Genet.

(1990)

J.M. Chirgwin et al.

Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease

Biochemistry

(1979)

A.F.W. Coulson et al.

Protein and nucleic acid sequence database searching: a suitable case for parallel processing

Computer J.

(1987)

A. Danek et al.

Normal dystrophin in McLeod myopathy

Ann. Neurol.

(1990)

A. Danek et al.

Cerebral involvement in McLeod syndrome

Neurology

(1994)

D.M. Engelman et al.

Identifying nonpolar transbilayer helices in amino acid sequences of membrane proteins

Annu. Rev. Biophys. Biophys. Chem.

(1986)

W.R. Galey et al.

Morphology and physiology of the McLeod erythrocyte. I. Scanning electron microscopy and electrolyte and water transport properties

Vox Sang.

(1978)

C.R. Gerfen et al.

D₁ and D₂ dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons

Science

(1990)

J. Guastella et al.

Cloning and expression of a rat brain GABA transporter

Science

(1990)

R. Hardie

Acanthocytosis and neurological impairment - a review

Q. J. Med.

(1989)

E. Hartmann et al.

Predicting the orientation of eukaryotic membrane-spanning proteins

Cited by (245)

Acupuncture for treating symptoms associated with chorea-acanthocytosis: A CARE-compliant case report
2023, Explore
Chorea-acanthocytosis (ChAc) is the most common type of neuroacanthocytosis syndromes. Characteristic movement disorders of ChAc are choreiform movements affecting both trunk and extremities. Acanthocytosis in peripheral blood smear, elevated serum creatine kinase, atrophy of heads of caudate nuclei and dilation of the anterior horn of the lateral ventricles in magnetic resonance imaging could assist the diagnosis of ChAc.
We aimed to report on the use of acupuncture to successfully improve ChAc symptoms.
A patient with definite ChAc was admitted, who had suffered from involuntary tongue protrusion for about 10 years. Acupuncture treatment was administrated for 3 times a week for 2 months. The chorea tremor control area, Baihui (GV20), Sishencong (EX-HN1), Shenting (GV24), Benshen (GB13, bilateral), Yintang (GV29), Neiguan (PC6, bilateral), Tongli (HT5, bilateral), Zusanli (ST36, bilateral), Sanyinjiao (SP6, bilateral), Dicang (ST4, bilateral), Chengjiang (CV24), Lianquan (CV23), Jinjin (EX-HN12) and Yuye (EX-HN13) were selected as acupunture points.
Previous drug dosage was reduced and the frequency of involuntary tongue protrusion was significantly reduced. Other clinical symptoms were also well controlled. Peripheral blood smear still indicated an increased proportion of red lineage, but blood analyses revealed improvement at follow-up.
For patients who do not response well to conventional medical treatments, acupuncture might be used as an alternative treatment for symptoms related to ChAc.
Insights into VPS13 properties and function reveal a new mechanism of eukaryotic lipid transport
2021, Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
The occurrence of protein mediated lipid transfer between intracellular membranes has been known since the late 1960's. Since these early discoveries, numerous proteins responsible for such transport, which often act at membrane contact sites, have been identified. Typically, they comprise a lipid harboring module thought to shuttle back and forth between the two adjacent bilayers. Recently, however, studies of the chorein domain protein family, which includes VPS13 and ATG2, has led to the identification of a novel mechanism of lipid transport between organelles in eukaryotic cells mediated by a rod-like protein bridge with a hydrophobic groove through which lipids can slide. This mechanism is ideally suited for bulk transport of bilayer lipids to promote membrane growth. Here we describe how studies of VPS13 led to the discovery of this new mechanism, summarize properties and known roles of VPS13 proteins, and discuss how their dysfunction may lead to disease.
Lipid Droplet Contact Sites in Health and Disease
2021, Trends in Cell Biology
After having been disregarded for a long time as inert fat drops, lipid droplets (LDs) are now recognized as ubiquitous cellular organelles with key functions in lipid biology and beyond. The identification of abundant LD contact sites, places at which LDs are physically attached to other organelles, has uncovered an unexpected level of communication between LDs and the rest of the cell. In recent years, many disease factors mutated in hereditary disorders have been recognized as LD contact site proteins. Furthermore, LD contact sites are dramatically rearranged in response to infections with intracellular pathogens, as well as under pathological metabolic conditions such as hepatic steatosis. Collectively, it is emerging that LD–organelle contacts are important players in development and progression of disease.
Current state of knowledge in Chorea-Acanthocytosis as core Neuroacanthocytosis syndrome
2018, European Journal of Medical Genetics
Neuroacanthocytosis (NA) syndromes are a group of rare diseases characterized by neurological disorders and misshaped spiky red blood cells (acanthocytes) including Chorea-Acanthocytosis (ChAc), McLeod syndrome (MLS), Huntington disease-like 2 (HDL 2), pantothenate kinase-associated neurodegeneration (PKAN), abeta- and hypobetalipoproteinemia and aceruloplasminemia. This clinically and genetically heterogeneous group of diseases shares main clinical features presenting most often as a hyperkinetic movement disorder. Even though these are long noted disease conditions, we still know only little on the underlying disease mechanisms.
The current review focuses upon ChAc as the core entity of NA syndromes caused by mutations in the VPS13A gene. The support of patient organizations and the ERA-NET initiative yielded to different multidisciplinary efforts with significant progress on our understanding of ChAc. Disturbances in two pathways are currently considered to be significantly involved in the pathophysiology of ChAc, namely elevated Lyn kinase phosphorylation and decreased signaling via Phosphoinositide 3-kinase (PI3K). These recent developments may reveal potential drugable targets for causative therapies of ChAc.
Multisystem pathology in McLeod syndrome
2024, Neuropathology
Erythroid Differentiation Dependent Interaction of VPS13A with XK at the Plasma Membrane of K562 Cells
2023, Contact

View all citing articles on Scopus

View full text

Cell

ArticleIsolation of the gene for McLeod syndrome that encodes a novel membrane transport protein

Abstract

J. Mol. Biol.

J. Biol. Chem.

J. Biol. Chem.

Trends Neurosci

Biochem. Biophys. Res. Commun.

Trends Biochem. Sci.

J. Biol. Chem.

J. Biol. Chem.

J. Mol. Biol.

FEBS Lett.

Blood

J. Biol. Chem.

Meth. Enzymol.

J. Biol. Chem.

Cell

Trends Neurosci.

Trends Pharmacol.

J. Biol. Chem.

Neurotransmitter transporters: recent progress

Annu. Rev. Neurosci.

The direct screening of cosmid libraries with yeast artificial chromosomes

Nucl. Acidś Res.

Localization of the McLeod locus (XK) within Xp21 by deletion analysis

Am. J. Hum. Genet.

CpG-rich islands and the function of DNA methylation

Nature

Cloning and expression of a functional serotonin transporter from rat brain

Nature

Studies of sarcolemmal integrity in myopathic muscle

Neurology

Hypothesis about the function of membrane-buried proline residues in transport proteins

Resonance raman studies of visual pigments

Annu. Rev. Biophys. Bioeng.

Duchenne muscular dystrophy: plasma membrane loss initiates muscle cell necrosis unless it is repaired

Brain

Dystrophin expression and genotypic analysis of two cases of benign X-linked myopathy (McLeod's syndrome)

J. Med. Genet.

Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease

Biochemistry

Protein and nucleic acid sequence database searching: a suitable case for parallel processing

Computer J.

Normal dystrophin in McLeod myopathy

Ann. Neurol.

Cerebral involvement in McLeod syndrome

Neurology

Identifying nonpolar transbilayer helices in amino acid sequences of membrane proteins

Annu. Rev. Biophys. Biophys. Chem.

Morphology and physiology of the McLeod erythrocyte. I. Scanning electron microscopy and electrolyte and water transport properties

Vox Sang.

D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons

Science

Cloning and expression of a rat brain GABA transporter

Science

Acanthocytosis and neurological impairment - a review

Q. J. Med.

Predicting the orientation of eukaryotic membrane-spanning proteins

Article
Isolation of the gene for McLeod syndrome that encodes a novel membrane transport protein

D₁ and D₂ dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons