On 2013 Oct 01, Markus Meissner commented:

Dr Elena Jimenez-Ruis (Meissner lab):

The apicomplexan parasite Toxoplasma gondii employs secretory organelles; the micronemes, rhoptries and dense granules that are sequentially secreted during the invasion process. The knowledge on the evolution biogenesis, maintenance and regulation of these unique organelles is insufficient. The present paper describes the function of the sortilin-like receptor (TgSORTLR) in the vesicular trafficking within this parasite. This protein was previously described by the authors as a transmembrane protein with a luminal cargo-binding domain (Fauquenoy et al., 2008). In this study, the transmembrane protein was colocalised with Golgi and endolysosomal system. Although, sometimes difficult to judge based on the provided images, the authors demonstrate a co-localisation of TgSORTLR with known markers of the Golgi and endosomal like compartments. The authors suggest that this protein is involved in the endocytic/exocytic system in T. gondii.However, to date endocytosis in T. gondii remains unclear. Importantly, TgSORTLR coprecipitates with micronemeal and rhoptry proteins, suggesting that TgSORTLR is a cargo receptor for ROP and MIC proteins between Golgi and endolysosomal system. Strikingly, in a conditional knockdown mutant micronemal and rhoptry proteins are mislocalised and appear to enter the constitutive secretory pathway. In electron microscopy a lack of micronemes and rhoptries has been confirmed in this mutant. Overall, this very nice study significantly contributes to broaden our understanding of the secretory pathway in T. gondii parasites. TgSORTLR is important for the correct delivery of the microneme and rhoptry proteins to their respective organelles . However, the question why the parasite stops their replication and seems to die after the ablation of TgSORTLR should be addressed in the future. The authors focus a lot on micronemal and rhoptry proteins, which they identify as interactants in co-IPs. However, this does not exclude other cargo that travels through the endosomes in TgSORTLR dependent manner. A more thorough analysis of the inner membrane complex, apicoplast and nuclear division would be helpful in the future. For example dominant negative expression of TgSORTLR appears to have a clear effect on parasite replication (see Fig. 2, where several parasitophorous vacuoles with only 3 nuclei are shown). However, this effect cannot be due to ablation of micronemes and or rhoptry biogenesis, since in this case no major replication defect is obvious (see Breinich et al., 2009; Beck et al., 2013 or Mueller et al., 2013).

On 2013 Oct 01, Markus Meissner commented:

Dr Elena Jimenez-Ruis (Meissner lab):

The apicomplexan parasite Toxoplasma gondii employs secretory organelles; the micronemes, rhoptries and dense granules that are sequentially secreted during the invasion process. The knowledge on the evolution biogenesis, maintenance and regulation of these unique organelles is insufficient. The present paper describes the function of the sortilin-like receptor (TgSORTLR) in the vesicular trafficking within this parasite. This protein was previously described by the authors as a transmembrane protein with a luminal cargo-binding domain (Fauquenoy et al., 2008). In this study, the transmembrane protein was colocalised with Golgi and endolysosomal system. Although, sometimes difficult to judge based on the provided images, the authors demonstrate a co-localisation of TgSORTLR with known markers of the Golgi and endosomal like compartments. The authors suggest that this protein is involved in the endocytic/exocytic system in T. gondii.However, to date endocytosis in T. gondii remains unclear. Importantly, TgSORTLR coprecipitates with micronemeal and rhoptry proteins, suggesting that TgSORTLR is a cargo receptor for ROP and MIC proteins between Golgi and endolysosomal system. Strikingly, in a conditional knockdown mutant micronemal and rhoptry proteins are mislocalised and appear to enter the constitutive secretory pathway. In electron microscopy a lack of micronemes and rhoptries has been confirmed in this mutant. Overall, this very nice study significantly contributes to broaden our understanding of the secretory pathway in T. gondii parasites. TgSORTLR is important for the correct delivery of the microneme and rhoptry proteins to their respective organelles . However, the question why the parasite stops their replication and seems to die after the ablation of TgSORTLR should be addressed in the future. The authors focus a lot on micronemal and rhoptry proteins, which they identify as interactants in co-IPs. However, this does not exclude other cargo that travels through the endosomes in TgSORTLR dependent manner. A more thorough analysis of the inner membrane complex, apicoplast and nuclear division would be helpful in the future. For example dominant negative expression of TgSORTLR appears to have a clear effect on parasite replication (see Fig. 2, where several parasitophorous vacuoles with only 3 nuclei are shown). However, this effect cannot be due to ablation of micronemes and or rhoptry biogenesis, since in this case no major replication defect is obvious (see Breinich et al., 2009; Beck et al., 2013 or Mueller et al., 2013).