LRGUK1 is part of a multiprotein complex required for manchette function and male fertility
Date
2017
Authors
Okuda, H.
DeBoer, K.
O'Connor, A.E.
Merriner, D.J.
Jamsai, D.
O'Bryan, M.K.
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Journal article
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The FASEB Journal, 2017; 31(3):1141-1152
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Hidenobu Okuda, Kathleen DeBoer, Anne E. O’Connor, D. Jo Merriner, Duangporn Jamsai, and Moira K. O’Bryan
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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, via the 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.
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© FASEB