Microtubule number and length determine cellular shape and function in Plasmodium

• Published in: The EMBO journal Vol. 38; no. 15; p. e100984
• Main Authors: Spreng, Benjamin, Fleckenstein, Hannah, Kübler, Patrick, Di Biagio, Claudia, Benz, Madlen, Patra, Pintu, Schwarz, Ulrich S, Cyrklaff, Marek, Frischknecht, Friedrich
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 01.08.2019
• Subjects: Animals; Gene Deletion; Malaria - parasitology; Mice; Models, Theoretical; Plasmodium - genetics; Plasmodium - metabolism; Plasmodium - pathogenicity; Protozoan Proteins - genetics; Protozoan Proteins - metabolism; Sporozoites - genetics; Sporozoites - growth & development; Sporozoites - pathogenicity; Tubulin - genetics; Tubulin - metabolism; infection; sporozoite; microtubules; malaria; cell morphogenesis
• ISSN: 0261-4189; 1460-2075
• DOI: 10.15252/embj.2018100984

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.