Characterization of membrane occupation and recognition nexus repeat containing 3, meiosis expressed gene 1 binding partner, in mouse male germ cells

Zhang, Ling; Shang, Xue‐Jun; Li, Hongfei; Shi, Yuqin; Wei, Li; Teves, María E.; Wang, Zhi-Qiong; Jiang, Gaofeng; Song, Shuo; Zhang, Zhibing

doi:10.4103/1008-682x.138186

Cited by 19 publications

(18 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Function of the gene product, membrane occupation and recognition nexus repeat containing 3 (MORN3), has not been functionally characterized. However in mice, from its specific expression in testis and its property of binding to meiosis expressed gene 1 (Meg1), a regulator of spermatogenesis, it has been suggested that Morn3 also plays a role in sperm formation [ 44 ]. Based on this suspected biology, currently there is little evidence to consider MORN3 as a candidate gene in KD susceptibility.…”

Section: Discussionmentioning

confidence: 99%

Variations in ORAI1 Gene Associated with Kawasaki Disease

et al. 2016

View full text Add to dashboard Cite

Kawasaki disease (KD; MIM#61175) is a systemic vasculitis syndrome with unknown etiology which predominantly affects infants and children. Recent findings of susceptibility genes for KD suggest possible involvement of the Ca2+/NFAT pathway in the pathogenesis of KD. ORAI1 is a Ca2+ release activated Ca2+ (CRAC) channel mediating store-operated Ca2+ entry (SOCE) on the plasma membrane. The gene for ORAI1 is located in chromosome 12q24 where a positive linkage signal was observed in our previous affected sib-pair study of KD. A common non-synonymous single nucleotide polymorphism located within exon 2 of ORAI1 (rs3741596) was significantly associated with KD (P = 0.028 in the discovery sample set (729 KD cases and 1,315 controls), P = 0.0056 in the replication sample set (1,813 KD cases vs. 1,097 controls) and P = 0.00041 in a meta-analysis by the Mantel-Haenszel method). Interestingly, frequency of the risk allele of rs3741596 is more than 20 times higher in Japanese compared to Europeans. We also found a rare 6 base-pair in-frame insertion variant associated with KD (rs141919534; 2,544 KD cases vs. 2,414 controls, P = 0.012). These data indicate that ORAI1 gene variations are associated with KD and may suggest the potential importance of the Ca2+/NFAT pathway in the pathogenesis of this disorder.

show abstract

Section: Discussionmentioning

confidence: 99%

Variations in ORAI1 Gene Associated with Kawasaki Disease

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Besides PACRG and SPAG16L, MEIG1 also associates with transcription factor-like 5 protein (TCFL5) ( Shi et al, 2013 ), and membrane occupation and recognition nexus repeat-containing 3 (MORN3) (Zhang et al, 2014). Interestingly, both TCFL5 and MORN3 are present in the manchette, and MORN3 localization is dependent on MEIG1 ( Zhang et al, 2014 ). These proteins may modulate MEIG1/PACRG function.…”

Section: Discussionmentioning

confidence: 99%

A MEIG1/PACRG complex in the manchette is essential for building the sperm flagella

Tang

Teves

et al. 2015

Development

Self Cite

View full text Add to dashboard Cite

A key event in the process of spermiogenesis is the formation of the flagella, which enables sperm to reach eggs for fertilization. Yeast two-hybrid studies revealed that meiosis-expressed gene 1 (MEIG1) and Parkin co-regulated gene (PACRG) interact, and that sperm-associated antigen 16, which encodes an axoneme central apparatus protein, is also a binding partner of MEIG1. In spermatocytes of wild-type mice, MEIG1 is expressed in the whole germ cell bodies, but the protein migrates to the manchette, a unique structure at the base of elongating spermatid that directs formation of the flagella. In the elongating spermatids of wild-type mice, PACRG colocalizes with α-tubulin, a marker for the manchette, whereas this localization was not changed in the few remaining elongating spermatids of Meig1-deficient mice. In addition, MEIG1 no longer localizes to the manchette in the remaining elongating spermatids of Pacrg-deficient mice, indicating that PACRG recruits MEIG1 to the manchette. PACRG is not stable in mammalian cells, but can be stabilized by MEIG1 or by inhibition of proteasome function. SPAG16L is present in the spermatocyte cytoplasm of wild-type mice, and in the manchette of elongating spermatids, but in the Meig1 or Pacrg-deficient mice, SPAG16L no longer localizes to the manchette. By contrast, MEIG1 and PACRG are still present in the manchette of Spag16L-deficient mice, indicating that SPAG16L is a downstream partner of these two proteins. Together, our studies demonstrate that MEIG1/PACRG forms a complex in the manchette and that this complex is necessary to transport cargos, such as SPAG16L, to build the sperm flagella.

show abstract

“…61 MORN3, expressed in the manchette of the elongating spermatid, was recently identified as another MEIG1-interacting protein. 62 …”

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

Characterization of membrane occupation and recognition nexus repeat containing 3, meiosis expressed gene 1 binding partner, in mouse male germ cells

Cited by 19 publications

References 40 publications

Variations in ORAI1 Gene Associated with Kawasaki Disease

Variations in ORAI1 Gene Associated with Kawasaki Disease

A MEIG1/PACRG complex in the manchette is essential for building the sperm flagella

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

Contact Info

Product

Resources

About