Microtubule number and length determine cellular shape and function in Plasmodium. (24th May 2019)

• Record Type: Journal Article
• Authors: Spreng, Benjamin; Fleckenstein, Hannah; Kübler, Patrick; Di Biagio, Claudia; Benz, Madlen; Patra, Pintu; Schwarz, Ulrich S; Cyrklaff, Marek; Frischknecht, Friedrich
• Is Part Of: EMBO journal. Volume 38:Number 15(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-05-24
• Subjects: cell morphogenesis -- infection -- malaria -- microtubules -- sporozoite; Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.2018100984
• Languages: English
• ISSNs: 0261-4189

Abstract

Abstract: Microtubules are cytoskeletal filaments essential for many cellular processes, including establishment and maintenance of polarity, intracellular transport, division and migration. In most metazoan cells, the number and length of microtubules are highly variable, while they can be precisely defined in some protozoan organisms. However, in either case the significance of these two key parameters for cells is not known. Here, we quantitatively studied the impact of modulating microtubule number and length in Plasmodium, the protozoan parasite causing malaria. Using a gene deletion and replacement strategy targeting one out of two α‐tubulin genes, we show that chromosome segregation proceeds in the oocysts even in the absence of microtubules. However, fewer and shorter microtubules severely impaired the formation, motility and infectivity of Plasmodium sporozoites, the forms transmitted by the mosquito, which usually contain 16 microtubules. We found that α‐tubulin expression levels directly determined the number of microtubules, suggesting a high nucleation barrier as supported by a mathematical model. Infectious sporozoites were only formed in parasite lines featuring at least 10 microtubules, while parasites with 9 or fewer microtubules failed to transmit. Synopsis: The number and length of microtubules are highly variable within metazoan cells. This study reveals that tuning the number and the length of cytoplasmic microtubules affects the formation, infectivity, and length of sporozoites of the protozoan parasite Plasmodium . Depletion of microtubules in Plasmodium does not inhibit chromosome segregation. Reducing the number and length of microtubules reduces cell size and decreases infectivity of sporozoites. Mathematical modeling predicts that tubulin expression levels dictate microtubule number rather than length, because nucleation rate is higher than elongation rate. Abstract : A combination of gene deletion, gene replacement and mathematical modeling analyses reveals the organismal consequences of altering the number and length of microtubules.