KIF1-binding protein interacts with KIF3A in haploid male germ cells

Lehti, Mari S.; Kotaja, Noora; Sironen, Anu

doi:10.1530/rep-15-0173

Cited by 9 publications

(4 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Phenocopying Mns1 −/− , a germ cell-specific depletion of Kif3a , affects sperm tail formation, manchette organization and the shaping of sperm heads. 56 KIF3A also interacts with a KIF1-binding protein (KBP) in the manchette of elongating spermatids 57 ; however, the role of KBP in spermatid elongation remains unknown.…”

Section: Manchette Of Elongating Spermatidsmentioning

confidence: 99%

The control of male fertility by spermatid-specific factors: searching for contraceptive targets from spermatozoon’s head to tail

et al. 2016

View full text Add to dashboard Cite

Male infertility due to abnormal spermatozoa has been reported in both animals and humans, but its pathogenic causes, including genetic abnormalities, remain largely unknown. On the other hand, contraceptive options for men are limited, and a specific, reversible and safe method of male contraception has been a long-standing quest in medicine. Some progress has recently been made in exploring the effects of spermatid-specifical genetic factors in controlling male fertility. A comprehensive search of PubMed for articles and reviews published in English before July 2016 was carried out using the search terms ‘spermiogenesis failure', ‘globozoospermia', ‘spermatid-specific', ‘acrosome', ‘infertile', ‘manchette', ‘sperm connecting piece', ‘sperm annulus', ‘sperm ADAMs', ‘flagellar abnormalities', ‘sperm motility loss', ‘sperm ion exchanger' and ‘contraceptive targets'. Importantly, we have opted to focus on articles regarding spermatid-specific factors. Genetic studies to define the structure and physiology of sperm have shown that spermatozoa appear to be one of the most promising contraceptive targets. Here we summarize how these spermatid-specific factors regulate spermiogenesis and categorize them according to their localization and function from spermatid head to tail (e.g., acrosome, manchette, head-tail conjunction, annulus, principal piece of tail). In addition, we emphatically introduce small-molecule contraceptives, such as BRDT and PPP3CC/PPP3R2, which are currently being developed to target spermatogenic-specific proteins. We suggest that blocking the differentiation of haploid germ cells, which rarely affects early spermatogenic cell types and the testicular microenvironment, is a better choice than spermatogenic-specific proteins. The studies described here provide valuable information regarding the genetic and molecular defects causing male mouse infertility to improve our understanding of the importance of spermatid-specific factors in controlling fertility. Although a male contraceptive ‘pill' is still many years away, research into the production of new small-molecule contraceptives targeting spermatid-specific proteins is the right avenue.

show abstract

Section: Manchette Of Elongating Spermatidsmentioning

confidence: 99%

The control of male fertility by spermatid-specific factors: searching for contraceptive targets from spermatozoon’s head to tail

et al. 2016

View full text Add to dashboard Cite

show abstract

“…In addition, KBP gene copy number has been recently reported as predictive in paediatric neuroblastoma prognosis, prompting its suggestion as a drug target 16 . KBP was originally identified as a kinesin-3 binding partner that modulated its mitochondrial transport function 8 ; however, KBP has since been shown to interact with a subset of other kinesin family members to regulate diverse cellular processes including mitosis 17,18 , spermatogenesis 19 and neuronal differentiation, growth and cargo distribution 10,[20][21][22][23][24] .…”

Section: Introductionmentioning

confidence: 99%

The mechanism of kinesin inhibition by kinesin-binding protein

Atherton

Hummel

Olieric

et al. 2020

eLife

View full text Add to dashboard Cite

Subcellular compartmentalisation is necessary for eukaryotic cell function. Spatial and temporal regulation of kinesin activity is essential for building these local environments via control of intracellular cargo distribution. Kinesin binding protein (KBP) interacts with a subset of kinesins via their motor domains, inhibits their microtubule (MT) attachment and blocks their cellular function. However, its mechanisms of inhibition and selectivity have been unclear. Here we use cryo-electron microscopy to reveal the structure of KBP and of a KBP-kinesin motor domain complex. KBP is a TPR-containing, right-handed α-solenoid that sequesters the kinesin motor domain’s tubulin-binding surface, structurally distorting the motor domain and sterically blocking its MT attachment. KBP uses its α-solenoid concave face and edge loops to bind the kinesin motor domain, and selected structure-guided mutations disrupt KBP inhibition of kinesin transport in cells. The KBP-interacting motor domain surface contains motifs exclusively conserved in KBP-interacting kinesins, suggesting a basis for kinesin selectivity.

show abstract

“…KIF3A is an important regulator of spermatogenesis and plays a crucial role in maintaining male fertility (7). KIF3A interacts with a KIF1-binding protein (KBP) in the mouse testis, and KBP may play a role in spermatid elongation and in the function of the late chromatoid body (8).…”

mentioning

confidence: 99%