This discrepancy has been explained as leaky expression of the respective gene of interest. Intriguingly, all mutants generated for the core components of the invasion machinery remained capable of invading the host cells, despite the absence of elements thought to control the function of the actin/myoA-based motor, and even in the absence of actin itself. While compensatory or redundancy mechanisms are likely for some of these mutants, in particular for the myosins, these results also open the possibility of alternative molecular pathways to account for gliding motility and host cell invasion. In addition host cell egress was completely blocked and therefore isolation of a clonal mlc1 KO population was not possible. Of note, since MLC1 depletion triggered MyoA mislocalisation, functional redundancy in the repertoire of myosin light chains is unlikely. In good agreement, depletion of MTIP in Plasmodium berghei results in degradation of MyoA. However, based on these results the presence of a different motor complex that can substitute for MyoA, such as MyoD-MLC2 cannot be excluded. GAP45 depletion had a major effect on the shape of extracellular parasites, which lost their typical crescent shape and rounded up. This morphological change was accompanied by the redistribution of MLC1 and MyoA to the cytosol of the parasites. While these results confirm previous results by Frenal et al. 2010, it was surprising to find that even morphologically disrupted gap45 KO parasites were capable of gliding, albeit slower than controls. Strikingly, we found that gap45 KO parasites glided more efficiently than myoA KO parasites, confirming that motility can be generated in the absence of the known motor complex. Although it is possible that a different, unknown myosin motor is involved in this process, one has to consider that the IMC, the platform for a potential second motor, is disrupted in gap45 KO parasites. Finally, invasion by GAP45 depleted parasites was significantly reduced, probably as a consequence of the morphological defect, but not of the loss of gliding motility. Importantly, as described for mlc1 KO and myoA KO parasites, host cell entry proceeded through a normal TJ. Similar to mlc1 KO parasites long-term cultivation of gap45 KO parasites was not possible – most likely because of a block in host cell egress. Intriguingly, depletion of Echinatin parasite actin did not result in a complete block of motility, since short circular trails were readily detected in motility assays, suggesting that a residual motility is possible even in the absence of parasite actin. As is the case for motility, depletion of the core components of the known invasion machinery did not result in a block of host cell invasion. Instead it appears that the major limitation caused by depletion of this machinery lies in the delayed formation of the TJ. In the case of myoA KO parasites and act1 KO parasites TJ formation was severely delayed, explaining a reduction in Ergosterol overall invasion rate. However, once the TJ was formed, parasites entered the host cell regardless of the integrity of the typical invasion machinery. As demonstrated for myoA KO parasites, the entry process was less efficient, with many parasites moving into the host cell in a stop-and-go fashion. However, since some parasites could enter host cells at the same speed as control parasites, it is possible that the parasite or the host cell can generate the force required for entry. Together these results suggest that gliding motility is critical 
in a step upstream of TJ formation.