Abstract
Post-translational modifications (PTMs) allow proteins to regulate their structure, localisation and function in response to cell intrinsic and environmental signals. The diversity and number of modifications on proteins increase the complexity of cellular proteomes by orders of magnitude. Several proteomic and molecular studies have revealed an abundance of PTMs in malaria parasite proteome, where mediators of PTMs play crucial roles in parasite pathogenesis and transmission. In this article, we discuss recent findings in asexual stages of ten diverse PTMs and investigate whether these proteins are expressed in sexual stages. We discovered 25–50 % of proteins exhibiting post-translational modifications in asexual stages are also expressed in sexual stage gametocytes. Moreover we analyse the function of the modified proteins shared with the gametocyte proteome and try to encourage the scientific community to investigate the roles of diverse PTMs beyond phosphorylation in sexual stages which could not only reveal unique aspects of parasite biology, but also uncover new avenues for transmission blocking.
Highlights
Malaria maintains a high global disease burden, threatening the health of millions of people
A majority of the studies have focussed on the asexual blood stages of the parasite and phosphorylation is the sole Post-translational modifications (PTMs) of non-histone proteins examined in sexual stage gametocytes [3,4]
We discovered a significant proportion of proteins identified in PTM studies in the asexual parasites were detected in the gametocyte proteome suggesting these proteins could be putatively modified in gametocytes and regulate parasite transmission (Table 1 and Supplementary Table 2)
Summary
Malaria maintains a high global disease burden, threatening the health of millions of people. Completion of the parasite’s life cycle requires both a vertebrate host (asexual stage) where it causes disease and a mosquito vector (sexual stage) which is essential for parasite transmission. Upon ingestion during a mosquito bloodmeal, specialised transmission-competent parasites (male and fe male gametocyte cells) respond to rapid environmental changes in the mosquito gut where tight regulation of the parasite’s DNA replication, protein translation, cell morphological changes, and energy metabolism is essential for the parasite’s life-cycle transition into the vector (Fig. 1). Do PTMs on proteins exponentially expand the functional outputs from a gene, the dynamicity conferred by these modifications permit quick responses to changing environments. A majority of the studies have focussed on the asexual blood stages of the parasite and phosphorylation is the sole PTM of non-histone proteins examined in sexual stage gametocytes [3,4]. Beyond phosphorylation, the possible function of PTMs in transmission
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