PMID- 10559218
OWN - NLM
STAT- MEDLINE
DCOM- 19991214
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 47
DP  - 1999 Nov 19
TI  - Mutations in novel organic cation transporter (OCTN2), an organic
      cation/carnitine transporter, with differential effects on the organic cation
      transport function and the carnitine transport function.
PG  - 33388-92
AB  - Novel organic cation transporter (OCTN2) is an organic cation/carnitine
      transporter, and two missense mutations, L352R and P478L, in OCTN2 have been
      identified as the cause for primary carnitine deficiency. In the present study,
      we assessed the influence of these two mutations on the carnitine transport
      function and the organic cation transport function of OCTN2. The L352R mutation
      resulted in a complete loss of both transport functions. In contrast, the P478L
      mutation resulted in a complete loss of only the carnitine transport function but
      significantly stimulated the organic cation transport function. Studies with
      human OCTN2/rat OCTN2 chimeric transporters indicated that the carnitine
      transport site and the organic cation transport site were not identical. Because 
      carnitine transport is Na(+)-dependent whereas organic cation transport is
      Na(+)-independent, we investigated the possibility that the P478L mutation
      affected Na(+) binding. The Na(+) activation kinetics were found to be similar
      for the P478L mutant and wild type OCTN2. We then mutated nine different tyrosine
      residues located in or near transmembrane domains and assessed the transport
      function of these mutants. One of these mutations, Y211F, was found to have
      differential influence on the two transport activities of OCTN2 as did the P478L 
      mutation. However, the Na(+) activation kinetics were not affected. These
      findings are of clinical relevance to patients with primary carnitine deficiency 
      because whereas each and every mutation in these patients is expected to result
      in the loss of the carnitine transport function, all of these mutations may not
      interfere with the organic cation transport function.
FAU - Seth, P
AU  - Seth P
AD  - Department of Biochemistry, Medical College of Georgia, Augusta, Georgia 30912,
      USA.
FAU - Wu, X
AU  - Wu X
FAU - Huang, W
AU  - Huang W
FAU - Leibach, F H
AU  - Leibach FH
FAU - Ganapathy, V
AU  - Ganapathy V
LA  - eng
GR  - DA 10045/DA/NIDA NIH HHS/United States
GR  - HD 33347/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Carrier Proteins)
RN  - 0 (Cations)
RN  - 0 (Membrane Proteins)
RN  - 0 (Organic Cation Transport Proteins)
RN  - 0 (SLC22A5 protein, human)
RN  - 0 (Solute Carrier Family 22 Member 5)
RN  - 0 (Tetraethylammonium Compounds)
RN  - 42HK56048U (Tyrosine)
RN  - S7UI8SM58A (Carnitine)
SB  - IM
MH  - Animals
MH  - Carnitine/*metabolism
MH  - Carrier Proteins/genetics/*metabolism
MH  - Cations
MH  - HeLa Cells
MH  - Humans
MH  - Ion Transport
MH  - Kinetics
MH  - Membrane Proteins/genetics/*metabolism
MH  - Mutagenesis, Site-Directed
MH  - *Organic Cation Transport Proteins
MH  - Rats
MH  - Solute Carrier Family 22 Member 5
MH  - Tetraethylammonium Compounds/metabolism
MH  - Tyrosine/metabolism
EDAT- 1999/11/24 00:00
MHDA- 1999/11/24 00:01
CRDT- 1999/11/24 00:00
PHST- 1999/11/24 00:00 [pubmed]
PHST- 1999/11/24 00:01 [medline]
PHST- 1999/11/24 00:00 [entrez]
AID - 10.1074/jbc.274.47.33388 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Nov 19;274(47):33388-92. doi: 10.1074/jbc.274.47.33388.