TY - JOUR
T1 - NDRG1 interacts with APO A-I and A-II and is a functional candidate for the HDL-C QTL on 8q24
AU - Hunter, M.
AU - Angelicheva, Dora
AU - Tournev, I.
AU - Ingley, Evan
AU - Chan, Dick
AU - Watts, Gerald
AU - Kremensky, I.
AU - Kalaydjieva, Luba
PY - 2005
Y1 - 2005
N2 - Hereditary Motor and Sensory Neuropathy Lom (HMSNL) is a severe autosomal recessive peripheral neuropathy, the most common form of demyelinating Charcot-Marie-Tooth (CMT) disease in the Roma (Gypsy) population. The mutated gene, N-myc downstream-regulated gene 1 (NDRG1), is widely expressed and has been implicated in a range of processes and pathways. To gain an insight into NDRG1 function we performed yeast two-hybrid screening and identified interacting proteins whose known functions suggest involvement in cellular trafficking. Further analyses, focusing on apolipoproteins A-I and A-II, confirmed their interaction with NDRG1 in mammalian cells and suggest a defect in Schwann cell lipid trafficking as a major pathogenetic mechanism in HMSNL. At the same time, the chromosomal location of NDRG1 coincides with a reported HDL-C QTL in humans and in mice. A putative role of NDRG I in the general mechanisms of HDL-mediated cholesterol transport was supported by biochemical studies of blood lipids, which revealed an association between the Gypsy founder mutation, R148X, and decreased HDL-C levels. (c) 2005 Elsevier Inc. All rights reserved.
AB - Hereditary Motor and Sensory Neuropathy Lom (HMSNL) is a severe autosomal recessive peripheral neuropathy, the most common form of demyelinating Charcot-Marie-Tooth (CMT) disease in the Roma (Gypsy) population. The mutated gene, N-myc downstream-regulated gene 1 (NDRG1), is widely expressed and has been implicated in a range of processes and pathways. To gain an insight into NDRG1 function we performed yeast two-hybrid screening and identified interacting proteins whose known functions suggest involvement in cellular trafficking. Further analyses, focusing on apolipoproteins A-I and A-II, confirmed their interaction with NDRG1 in mammalian cells and suggest a defect in Schwann cell lipid trafficking as a major pathogenetic mechanism in HMSNL. At the same time, the chromosomal location of NDRG1 coincides with a reported HDL-C QTL in humans and in mice. A putative role of NDRG I in the general mechanisms of HDL-mediated cholesterol transport was supported by biochemical studies of blood lipids, which revealed an association between the Gypsy founder mutation, R148X, and decreased HDL-C levels. (c) 2005 Elsevier Inc. All rights reserved.
U2 - 10.1016/j.bbrc.2005.05.050
DO - 10.1016/j.bbrc.2005.05.050
M3 - Article
C2 - 15922294
SN - 0006-291X
VL - 332
SP - 982
EP - 992
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -