ABCA5 resides in lysosomes, and ABCA5 knockout mice develop lysosomal disease-like symptoms.
ABCA5 is a member of the ABC transporter A subfamily, and a mouse orthologue (mABCA5) in newborn mouse brain and neural cells was identified by reverse transcription-PCR. Full-length cDNA cloning revealed that mABCA5 consists of 1,642 amino acid residues and that its putative structure is that of a full-type ABC transporter having two sets of six transmembrane segments and a nucleotide binding domain. Immunohistochemical studies revealed that mABCA5 is expressed in brain, lung, heart, and thyroid gland. A subcellular localization analysis showed that mABCA5 is a resident of lysosomes and late endosomes. Abca5(-)(/)(-) mice exhibited symptoms similar to those of several lysosomal diseases in heart, although no prominent abnormalities were found in brain or lung. They developed a dilated cardiomyopathy-like heart after reaching adulthood and died due to depression of the cardiovascular system. In addition, Abca5(-)(/)(-) mice also exhibited exophthalmos and collapse of the thyroid gland. Therefore, ABCA5 is a protein related to a lysosomal disease and plays important roles, especially in cardiomyocytes and follicular cells.
Kubo
Yoshiyuki
Y
Department of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047, Japan.
Sekiya
Sayaka
S
Ohigashi
Megumi
M
Takenaka
Chiemi
C
Tamura
Kyoko
K
Nada
Shigeyuki
S
Nishi
Tsuyoshi
T
Yamamoto
Akitsugu
A
Yamaguchi
Akihito
A
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000015:Abnormalities, Multiple / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D005094:Exophthalmos / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008247:Lysosomes / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D021381:Protein Transport; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013961:Thyroid Gland / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism
C501079:ABCA5 protein, mouse; D018528:ATP-Binding Cassette Transporters; D012333:RNA, Messenger; D013963:Thyroid Hormones