Malaria IMC1 Membrane Skeleton Proteins Operate Autonomously and Participate in Motility Independently of Cell Shape

Abstract

Plasmodium IMC1 (inner membrane complex 1) proteins comprise components of the subpellicular network, a lattice of intermediate filaments that form a structural part of the pellicle in the zoite stages of malaria parasites. Family members IMC1a and IMC1b are differentially expressed in sporozoites and ookinetes, respectively, but have functionally equivalent roles affecting cell morphology, strength, motility, and infectivity. Because of the coincident effects of previous imc1 gene disruptions on both zoite shape and locomotion, it has been impossible to ascribe a direct involvement in motility to these proteins. We show here that a third family member, IMC1h, has a distinct differential expression pattern and localizes to the pellicle of both ookinetes and sporozoites. Knock-out of IMC1h mimics the loss-of-function phenotypes of IMC1a and IMC1b in their respective life stages, indicating that IMC1 proteins could be operating co-dependently. By generating double null mutant parasites for IMC1h and IMC1b, we tested this hypothesis: double knock-out exacerbated the phenotypes of the single knock-outs in terms of ookinete strength, motility, and infectivity but did not further affect ookinete morphology. These findings provide the first genetic evidence that IMC1 proteins can function independently of each other and contribute to gliding motility independently of cell shape.

Origin, composition, organization and function of the inner membrane complex of Plasmodium falciparum gametocytes

“…Taken together these data suggest that the IMC plays an important structural role in each of the cellular remodelling events that drive parasite elongation. This is consistent with recent work showing that specific IMC proteins can play roles in both motility and cell morphology (Tremp and Dessens, 2011).…”

Gliding motility in apicomplexan parasites

“…In addition to these scaffolding proteins and the anchoring components of the motility apparatus that reside in the IMC, many additional proteins are known to occupy the pellicle or IMC domain butmost have yet to be characterized. [20][21][22].The importance of pellicle architecture in structurally supporting normal parasite motility has been demonstrated by several studies in which disruption of pellicle components has led to altered gliding behavior [23][24][25][26].…”

The Plasmodium alveolin IMC1a is stabilised by its terminal cysteine motifs and facilitates sporozoite morphogenesis and infectivity in a dose-dependent manner

“…In the genus Plasmodium , 13 conserved and syntenic alveolin family members have been identified that are differentially expressed among the three different zoites stages of malaria parasites [7], [8]. It has been shown in the rodent malaria species P. berghei that disruption of alveolins gives rise to morphological aberrations that are accompanied by reduced tensile strength of the zoite stages in which they are found [5], [8], [9], [10], [11]. In Tetrahymena thermophila , knockdown of the alveolin Tt ALV2 was also reported to affect cell morphology [12], indicating that alveolin functions, like their structures, are evolutionary conserved.…”