Abstract
The synaptonemal complex (SC) is a supramolecular protein scaffold that mediates chromosome synapsis and facilitates crossing over during meiosis. In mammals, SC proteins are generally assumed to have no other function. Here, we show that SC protein TEX12 also localises to centrosomes during meiosis independently of chromosome synapsis. In somatic cells, ectopically expressed TEX12 similarly localises to centrosomes, where it is associated with centrosome amplification, a pathology correlated with cancer development. Indeed, TEX12 is identified as a cancer-testis antigen and proliferation of some cancer cells is TEX12-dependent. Moreover, somatic expression of TEX12 is aberrantly activated via retinoic acid signalling, which is commonly disregulated in cancer. Structure-function analysis reveals that phosphorylation of TEX12 on tyrosine 48 is important for centrosome amplification but not for recruitment of TEX12 to centrosomes. We conclude that TEX12 normally localises to meiotic centrosomes, but its misexpression in somatic cells can contribute to pathological amplification and dysfunction of centrosomes in cancers.
Highlights
The synaptonemal complex (SC) is a supramolecular protein scaffold that mediates chromosome synapsis and facilitates crossing over during meiosis
We report that meiotic synaptonemal complex protein TEX12 is frequently mis-expressed in cancer
We show that TEX12 has a previously overlooked localisation to the microtubule organising centres, in both meiosis and mitosis
Summary
The synaptonemal complex (SC) is a supramolecular protein scaffold that mediates chromosome synapsis and facilitates crossing over during meiosis. Ectopically expressed TEX12 localises to centrosomes, where it is associated with centrosome amplification, a pathology correlated with cancer development. Homologous chromosome pairs must become linked by crossovers in order to biorient on the meiosis-I spindle, adding an additional level of complexity relative to mitotic chromosome congression This complexity is reflected in a dedicated meiotic structure called the synaptonemal complex (SC). We show that mammalian SC protein TEX12, previously identified as a component of the SC central element, localises to centrosomes during meiosis in males, and upon ectopic expression in somatic cells. TEX12 can localise to centrosomes independently of other SC proteins, and its misexpression in somatic cells is associated with centrosome amplification through a mechanism that involves phosphorylation of a single conserved tyrosine, Y48. We propose a previously unappreciated localisation for TEX12 and uncover the drivers of its aberrant expression during tumorigenesis
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