Thyroid Hormones Transport 2
Thyroid Hormones

Author: Gianpiero Pescarmona
Date: 26/09/2009

Description

Plasma Transport

Plasma Membrane Transporters

BOTH TRANSLATION START SITES IN THE HUMAN MCT8
GENE ARE USED TO PRODUCE TWO MCT8 PROTEIN
ISOFORMS IN VITRO
E. C. FRIESEMA, W. E. VISSER, T. J. VISSER
Internal Medicine, Erasmus MC, Rotterdam, Netherlands
MCT8 is an important thyroid hormone transporter as mutations are
associated with severe psychomotor retardation and elevated serum
T3 levels with low to normal fT4 levels. MCT8 knockout mice show
the same changes in thyroid parameters, but lack the neurological
defects. The human (h) MCT8 gene contains two possible translation
start sites (TLSs). However, mouse MCT8 has only one TLS, which
corresponds to the second TLS in hMCT8. So far, we have only
studied the hMCT8 protein generated from the second TLS. mRNA
expression data from human liver revealed the presence of mRNA
species containing both TLSs. Long hMCT8 cDNA was constructed
by extending the 50-end of our short hMCT8 cDNA with a 312 bp
fragment. Transport studies were performed in transiently transfected
COS1 cells using both hMCT8 constructs. We found that T3
uptake in cells transfected with long hMCT8 was only 12% lower than
in cells with short hMCT8. Western blotting showed that transfection
with long hMCT8 gives rise to two hMCT8 protein bands of 61 and
69 kDa, the latter being more abundant than the former. The 61 kDa
band represents short hMCT8 (539 amino acids) and the 69 kDa band
represents long hMCT8 (613 amino acids). These results suggest that
long hMCT8 is capable of transporting thyroid hormone, but to study
this more specifically, we are currently mutating the second TLS to
prevent the synthesis of short MCT8. We found that both TLSs in the
hMCT8 gene are used to produce two isoforms that may be differentially
expressed in human tissues. Our findings might also explain
the neurological differences between humans and mice with MCT8
mutations as the long hMCT8 that does not exist in mice might play
an important role in human brain development.

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