A variant very low density lipoprotein receptor lacking 84 base pairs of O-linked sugar domain in the human brain myelin.
The very low density lipoprotein receptor (VLDLR) was considered to specifically bind to VLDL rich apolipoprotein E (apoE). However, its distribution and functions in vivo have yet to be elucidated. In human and rat VLDLR, a variant form lacking 84 base pairs (bp) in O-linked sugar domain was noted but its significance was not initially understood. This study shows that the variant form of VLDLR coexists with full-length VLDLR in majority of tissues but is a major component in the white matter of human brain. The tissue distribution of a variant VLDLR was detected in myelin as well as in other tissues except for the liver with immunohistochemistry using a monoclonal antibody. This variant VLDLR is proposed to be functionally important for internalizing apoE in human brain. ApoE is associated with beta-amyloid in senile plaques and plays a role in the transport of the beta-amyloid. The presence of VLDLR in myelin may be one explanation as to why beta-amyloid does not accumulate in the white matter which is rich in VLDLR. Recently, evidences on VLDLR obtained mainly using knock-out or transfected mice suggest this receptor to be neither specific for VLDL nor functionally important in mammals. However, no variant form of VLDLR was found in any tissues of mouse. This variant form of VLDLR should thus be studied in greater detail using human tissues or cells.
Nakamura
Y
Y
Department of Pathology, St. Mary's Hospital, Tsubukuhon-machi 422, Kurume, Japan. naka@st-mary-med.or.jp
Yamamoto
M
M
Kumamaru
E
E
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D020029:Base Pairing; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry / Q000235:genetics; D002236:Carbohydrate Conformation; D002648:Child; D002675:Child, Preschool; D005333:Fetus; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008079:Lipoproteins, VLDL / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009186:Myelin Sheath / Q000235:genetics*; D009844:Oligosaccharides / Q000737:chemistry / Q000235:genetics*; D051381:Rats; D011973:Receptors, LDL / Q000737:chemistry / Q000235:genetics*
D008079:Lipoproteins, VLDL; D009844:Oligosaccharides; D011973:Receptors, LDL; C036053:VLDL receptor