Towler, M. C. et al. A novel short splice variant of the tumour suppressor LKB1 is required for spermiogenesis. Biochem. J. 416, 1-14

Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dundee, Scotland, UK.
Biochemical Journal (Impact Factor: 4.4). 10/2008; 416(1):1-14. DOI: 10.1042/BJ20081447
Source: PubMed


LKB1 was discovered as a tumour suppressor mutated in Peutz-Jeghers syndrome, and is a gene involved in cell polarity as well as an upstream protein kinase for members of the AMP-activated protein kinase family. We report that mammals express two splice variants caused by alternate usage of 3'-exons. LKB1(L) is the previously described form, while LKB1(S) is a novel form in which the last 63 residues are replaced by a unique 39-residue sequence lacking known phosphorylation (Ser(431)) and farnesylation (Cys(433)) sites. Both isoforms are widely expressed in rodent and human tissues, although LKB1(S) is particularly abundant in haploid spermatids in the testis. Male mice in which expression of Lkb1(S) is knocked out are sterile, with the number of mature spermatozoa in the epididymis being dramatically reduced, and those spermatozoa that are produced have heads with an abnormal morphology and are non-motile. These results identify a previously undetected variant of LKB1, and suggest that it has a crucial role in spermiogenesis and male fertility.

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Available from: Silvina Meroni, Mar 03, 2015
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    • "Thus, hypothermia increases AMPK phosphorylation and, hence its activity in vivo [2]. Although there are several AMPK-related protein kinases described in the germ cells of testes [46] [52] and in spermatozoa [51], only recently the functionality of AMPK has been associated with motility regulation [15] [43]. This evidence suggests that the freezing–thawing process can modify sperm AMPK activity resulting in changes in the overall function of post-thawed cells. "
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    • "Cell lysates (100 lg protein) were immunoprecipitated by incubation at 4 °C for 2 h on a roller mixer with 6 ll of anti-AMPKa1/a2 antibody coupled to protein G-Sepharose, and the immunoprecipitates assayed for AMPK using the AMARA peptide [22]. When AMPK activity was assayed in HEK-293 cells expressing recombinant FLAG-tagged c2 subunit, immunoprecipitation was performed using 7 ll of EZview Red anti-FLAG M2 affinity gel from Sigma [18] "
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    • "Previously, some studies including knockout mice suggested a crucial role of AMPK-related kinases in spermatozoa function [17] [18]. Thus, a new shorter isoform of the AMPK upstream kinase LKB1, called LKB1s, which is expressed predominantly in haploid sperm cells from mammal testes [17], is pointed to play an essential role in spermiogenesis and fertility (motility) in mice. Additionally, the branch of AMPK in the human quinome tree includes the " serine/threonine kinase testis specific " TSSK family. "
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