title: Postendocytotic trafficking of the follicle-stimulating hormone (FSH)-FSH receptor complex.
abstract: Although the fates of the internalized hormone-receptor complexes formed by the lutropin/choriogonadotropin and the TSH receptors have been examined in some detail, much less is known about the fate of the internalized FSH-FSH receptor (FSHR) complex. Using biochemical and imaging approaches we show here that the majority of the internalized FSH-FSHR complex accumulates in endosomes and subsequently recycles back to the cell surface where the bound, intact hormone dissociates back into the medium. Only small amounts of FSH and the FSHR are routed to a lysosomal degradation pathway, and the extent of FSH-induced down-regulation of the cell surface and total FSHR is minimal. This pathway was detected in heterologous (human kidney 293T) cells transfected with the rat (r) or human (h) FSHR as well as in a mouse Sertoli cell line (MSC-1) or a mouse granulosa cell line (KK-1) transfected with the rFSHR.Additional experiments using a series of C-terminal deletions of the rFSHR and the hFSHR showed that the recycling of the internalized FSH-FSHR complex and the extent of hFSH-induced down-regulation is dictated by a short stretch of amino acids present at the extreme C-terminal end of the receptor.We conclude that most of the internalized FSH-FSHR complex is recycled back to the cell surface, that this recycling pathway is highly dependent on amino acid residues present near the C terminus of the FSHR, and that it is an important determinant of the extent of down-regulation of the FSHR.
authors.affiliation: Department of Pharmacology, The University of Iowa, Iowa City, Iowa 52242-1109, USA.
authors.forename: Hanumanthappa
authors.initials: H
authors.lastname: Krishnamurthy
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kishi
authors.forename: Mei
authors.initials: M
authors.lastname: Shi
authors.forename: Colette
authors.initials: C
authors.lastname: Galet
authors.forename: Ravi Sankar
authors.initials: RS
authors.lastname: Bhaskaran
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirakawa
authors.forename: Mario
authors.initials: M
authors.lastname: Ascoli
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D006063:Chorionic Gonadotropin / Q000378:metabolism; D015536:Down-Regulation; D004705:Endocytosis; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D046911:Macromolecular Substances; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D021381:Protein Transport; D051381:Rats; D011962:Receptors, FSH / Q000819:agonists / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011967:Receptors, Gonadotropin / Q000378:metabolism; D017384:Sequence Deletion; D012708:Sertoli Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D006063:Chorionic Gonadotropin; D046911:Macromolecular Substances; D011962:Receptors, FSH; D011967:Receptors, Gonadotropin; D005640:Follicle Stimulating Hormone