On 2015 Mar 28, Markus Meissner commented:

Hi Juergen, Fully agree ! Will be great to see what happens when interactions are rapidly disrupted. This is one of the main caveats of current conditional systems....simply too slow for fast processes, such as gliding and invasion.

On 2015 Mar 24, Jürgen Bosch commented:

Thank you Markus for your positive feedback on our review. I think it will be crucial in the future to utilize chemical probes to study these invasion mechanisms in different parasites.

On 2015 Mar 18, Markus Meissner commented:

This is a very nice review by Boucher and Bosch, summarising our current knowledge of apicomplexan invasion pathways. In the first part of the review the authors focus on novel structural data of the individual complexes known to be involved in gliding motility and invasion, while in the second part the current data regarding potential, alternative invasion pathways are presented. While the authors favour the more “traditional” linear motor system, data from diverse groups have been openly discussed, although some of the arguments might need further clarification. For example, the authors do not mention one important feature of the GAP45-depleted parasites. In these parasites the integrity of the IMC is lost AND other motor components dissociate and mislocalise to the cytosol of the parasite. Yet, these parasites are still capable of moving and invading, although the anchorage for the motor complex is missing. In case of act1KO it is in our opinion unlikely that parasites still have sufficient actin for gliding motility and invasion yet not for egress or apicoplast replication. Furthermore, the controversy regarding the effect of CytoD on host or parasite actin (see Rynig and Remington, 1978; Dobrowolski et al., 1996; Gonzales et al., 2009) and recent data on the role of aldolase ( Shen et al., 2014 ) seriously undermine the original rationale for the linear motor model, and in our view suggest that the earlier data supporting the model should be treated with as much scrutiny as the recent data arguing against it.<br> I agree with the authors that findings in Toxoplasma cannot necessarily be directly transferred to Plasmodium. However, this is also the case for other apicomplexans, which have undoubtly different (or alternative) invasion mechanisms, such as Theileria or Cryptosporidium. Of note, Theileria has a well conserved AMA1, but doesn't form a tight junction. While Theileria might use AMA1 for “zippering” into the host cell, it doesn’t use it for force transmission, since invasion is independent of host AND parasite actin (Shaw, 1999). More experiments are required to make sense out of these sometimes conflicting data, which can at this point be interpreted in multiple ways, and we fully agree with the authors that we need an open, unbiased discussion in order to solve the puzzle.

On 2015 Mar 18, Markus Meissner commented:

This is a very nice review by Boucher and Bosch, summarising our current knowledge of apicomplexan invasion pathways. In the first part of the review the authors focus on novel structural data of the individual complexes known to be involved in gliding motility and invasion, while in the second part the current data regarding potential, alternative invasion pathways are presented. While the authors favour the more “traditional” linear motor system, data from diverse groups have been openly discussed, although some of the arguments might need further clarification. For example, the authors do not mention one important feature of the GAP45-depleted parasites. In these parasites the integrity of the IMC is lost AND other motor components dissociate and mislocalise to the cytosol of the parasite. Yet, these parasites are still capable of moving and invading, although the anchorage for the motor complex is missing. In case of act1KO it is in our opinion unlikely that parasites still have sufficient actin for gliding motility and invasion yet not for egress or apicoplast replication. Furthermore, the controversy regarding the effect of CytoD on host or parasite actin (see Rynig and Remington, 1978; Dobrowolski et al., 1996; Gonzales et al., 2009) and recent data on the role of aldolase ( Shen et al., 2014 ) seriously undermine the original rationale for the linear motor model, and in our view suggest that the earlier data supporting the model should be treated with as much scrutiny as the recent data arguing against it.<br> I agree with the authors that findings in Toxoplasma cannot necessarily be directly transferred to Plasmodium. However, this is also the case for other apicomplexans, which have undoubtly different (or alternative) invasion mechanisms, such as Theileria or Cryptosporidium. Of note, Theileria has a well conserved AMA1, but doesn't form a tight junction. While Theileria might use AMA1 for “zippering” into the host cell, it doesn’t use it for force transmission, since invasion is independent of host AND parasite actin (Shaw, 1999). More experiments are required to make sense out of these sometimes conflicting data, which can at this point be interpreted in multiple ways, and we fully agree with the authors that we need an open, unbiased discussion in order to solve the puzzle.

On 2015 Mar 24, Jürgen Bosch commented:

Thank you Markus for your positive feedback on our review. I think it will be crucial in the future to utilize chemical probes to study these invasion mechanisms in different parasites.