TY - JOUR
T1 - The extracellular domain of luteinizing hormone receptor dictates its efficiency of maturation
AU - Lin, Cindy Chan Juan
AU - Clouser, Christine
AU - Peegel, Helle
AU - Menon, Bindu
AU - Menon, K. M.J.
N1 - Funding Information:
Supported by NIH Grant HD06656.
PY - 2008/12/5
Y1 - 2008/12/5
N2 - The processing of luteinizing hormone receptor (LHR) shows marked differences in different species. While the human LHR is predominantly expressed as the mature, 90 kDa species, rat LHR exists mostly in the 70 kDa precursor form. Since the extracellular domain of the LHR is unusually large in comparison with other G protein-coupled receptors, the present studies examined the role of extracellular domain in its processing. FLAG-tagged chimeric LH receptors were constructed by substituting the extracellular domain of the human receptor in rat LHR (hrr) and the extracellular domain of the rat receptor in human LHR (rhh). The intracellular processing, ligand binding and recycling of the chimeric receptors were compared with that of the wild type receptors in 293T cells. The results showed that the human and rat LHR were expressed predominantly as 90 and 70 kDa species, respectively, as expected. The introduction of the rat extracellular domain into the human LHR (rhh) decreased the abundance of the mature form with an increase in the precursor form. Conversely, substitution of the extracellular domain of the rat LHR by the extracellular domain of the human LHR (hrr) led to an increase in the mature form with a corresponding decrease in the precursor form. Changes were also observed in the ligand binding and recycling of the wild type and chimeric receptors. These results suggest that the extracellular domain of the LHR is one of the determinants that confer its ability for proper maturation and cell surface expression.
AB - The processing of luteinizing hormone receptor (LHR) shows marked differences in different species. While the human LHR is predominantly expressed as the mature, 90 kDa species, rat LHR exists mostly in the 70 kDa precursor form. Since the extracellular domain of the LHR is unusually large in comparison with other G protein-coupled receptors, the present studies examined the role of extracellular domain in its processing. FLAG-tagged chimeric LH receptors were constructed by substituting the extracellular domain of the human receptor in rat LHR (hrr) and the extracellular domain of the rat receptor in human LHR (rhh). The intracellular processing, ligand binding and recycling of the chimeric receptors were compared with that of the wild type receptors in 293T cells. The results showed that the human and rat LHR were expressed predominantly as 90 and 70 kDa species, respectively, as expected. The introduction of the rat extracellular domain into the human LHR (rhh) decreased the abundance of the mature form with an increase in the precursor form. Conversely, substitution of the extracellular domain of the rat LHR by the extracellular domain of the human LHR (hrr) led to an increase in the mature form with a corresponding decrease in the precursor form. Changes were also observed in the ligand binding and recycling of the wild type and chimeric receptors. These results suggest that the extracellular domain of the LHR is one of the determinants that confer its ability for proper maturation and cell surface expression.
KW - Binding ability
KW - Extracellular domain
KW - LH receptor
KW - Recycling of receptor
UR - http://www.scopus.com/inward/record.url?scp=54449097406&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=54449097406&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2008.09.136
DO - 10.1016/j.bbrc.2008.09.136
M3 - Article
C2 - 18848524
AN - SCOPUS:54449097406
SN - 0006-291X
VL - 377
SP - 307
EP - 311
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -