title: LRGUK1 is part of a multiprotein complex required for manchette function and male fertility.
abstract: Infertility occurs in 1 in 20 young men and is idiopathic in origin in most. We have reported that the leucine-rich repeat (LRR) and guanylate kinase-like domain containing, isoform (LRGUK)-1 is essential for sperm head shaping,viathe manchette, and the initiation of sperm tail growth from the centriole/basal body, and thus, male fertility. Within this study we have used a yeast 2-hybrid screen of an adult testis library to identify LRGUK1-binding partners, which were then validated with a range of techniques. The data indicate that LRGUK1 likely achieves its function in partnership with members of the HOOK family of proteins (HOOK-1-3), Rab3-interacting molecule binding protein (RIMBP)-3 and kinesin light chain (KLC)-3, all of which are associated with intracellular protein transport as cargo adaptor proteins and are localized to the manchette. LRGUK1 consists of 3 domains; an LRR, a guanylate kinase (GUK)-like and an unnamed domain. In the present study, we showed that the GUK-like domain is essential for binding to HOOK2 and RIMBP3, and the LRR domain is essential for binding to KLC3. These findings establish LRGUK1 as a key component of a multiprotein complex with an essential role in microtubule dynamics within haploid male germ cells.-Okuda, H., DeBoer, K., O'Connor, A. E., Merriner, D. J., Jamsai, D., O'Bryan, M. K. LRGUK1 is part of a multiprotein complex required for manchette function and male fertility.
authors.affiliation: Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia; and.|Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Okuda
authors.affiliation: Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia; and.|Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: Kathleen
authors.initials: K
authors.lastname: DeBoer
authors.affiliation: Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia; and.|Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: Anne E
authors.initials: AE
authors.lastname: O'Connor
authors.affiliation: Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia; and.|Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: D Jo
authors.initials: DJ
authors.lastname: Merriner
authors.affiliation: Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia; and.|Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: Duangporn
authors.initials: D
authors.lastname: Jamsai
authors.affiliation: Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia; and moira.obryan@monash.edu.|Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia moira.obryan@monash.edu.
authors.forename: Moira K
authors.initials: MK
authors.lastname: O'Bryan
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000378:metabolism; D051528:Guanylate Kinases / Q000737:chemistry / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism*; D016547:Kinesins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D051381:Rats; D013087:Spermatids / Q000378:metabolism*
chemical_list: C546999:Hook2 protein, mouse; C000715693:Klc3 protein, mouse; C000715694:Klct protein, rat; D008869:Microtubule-Associated Proteins; D051528:Guanylate Kinases; D019204:GTP-Binding Proteins; D016547:Kinesins
keywords: cargo adaptor; elongating spermatids; intracellular transport; sperm; spermatogenesis