Matches in SemOpenAlex for { <https://semopenalex.org/work/W4385620996> ?p ?o ?g. }
- W4385620996 abstract "ABSTRACT In the apicomplexans, endocytosed cargos (e.g., hemoglobin) are trafficked to a specialized organelle for digestion. This follows a unique endocytotic process at the micropore/cytostome in these parasites. However, the mechanism underlying endocytic trafficking remains elusive, due to the repurposing of classical endocytic proteins for the biogenesis of apical organelles. To resolve this issue, we have exploited the genetic tractability of the model apicomplexan Toxoplasma gondii , which ingests host cytosolic materials (e.g., green fluorescent protein[GFP]). We determined an association between protein prenylation and endocytic trafficking, and using an alkyne-labeled click chemistry approach, the prenylated proteome was characterized. Genome editing, using clustered regularly interspaced short palindromic repaet/CRISPR-associated nuclease 9 (CRISPR/Cas9), was efficiently utilized to generate genetically modified lines for the functional screening of 23 prenylated candidates. This identified four of these proteins that regulate the trafficking of endocytosed GFP vesicles. Among these proteins, Rab1B and YKT6.1 are highly conserved but are non-classical endocytic proteins in eukaryotes. Confocal imaging analysis showed that Rab1B and Ras are substantially localized to both the trans-Golgi network and the endosome-like compartments in the parasite. Conditional knockdown of Rab1B caused a rapid defect in secretory trafficking to the rhoptry bulb, suggesting a trafficking intersection role for the key regulator Rab1B. Further experiments confirmed a critical role for protein prenylation in regulating the stability/activity of these proteins (i.e., Rab1B and YKT6.1) in the parasite. Our findings define the molecular basis of endocytic trafficking and reveal a potential intersection function of Rab1B on membrane trafficking in T. gondii . This might extend to other related protists, including the malarial parasites. IMPORTANCE The protozoan Toxoplasma gondii establishes a permissive niche, in host cells, that allows parasites to acquire large molecules such as proteins. Numerous studies have demonstrated that the parasite repurposes the classical endocytic components for secretory sorting to the apical organelles, leaving the question of endocytic transport to the lysosome-like compartment unclear. Recent studies indicated that endocytic trafficking is likely to associate with protein prenylation in malarial parasites. This information promoted us to examine this association in the model apicomplexan T. gondii and to identify the key components of the prenylated proteome that are involved. By exploiting the genetic tractability of T. gondii and a host GFP acquisition assay, we reveal four non-classical endocytic proteins that regulate the transport of endocytosed cargos (e.g., GFP) in T. gondii . Thus, we extend the principle that protein prenylation regulates endocytic trafficking and elucidate the process of non-classical endocytosis in T. gondii and potentially in other related protists." @default.
- W4385620996 created "2023-08-08" @default.
- W4385620996 creator A5001246506 @default.
- W4385620996 creator A5015152308 @default.
- W4385620996 creator A5017462387 @default.
- W4385620996 creator A5021689863 @default.
- W4385620996 creator A5026972489 @default.
- W4385620996 creator A5027576436 @default.
- W4385620996 creator A5027645285 @default.
- W4385620996 creator A5029764295 @default.
- W4385620996 creator A5048332389 @default.
- W4385620996 creator A5055640374 @default.
- W4385620996 creator A5066945142 @default.
- W4385620996 creator A5067908158 @default.
- W4385620996 creator A5071110237 @default.
- W4385620996 creator A5075380240 @default.
- W4385620996 creator A5076702757 @default.
- W4385620996 creator A5077546917 @default.
- W4385620996 creator A5078909568 @default.
- W4385620996 date "2023-08-07" @default.
- W4385620996 modified "2023-10-18" @default.
- W4385620996 title "Functional screening reveals <i>Toxoplasma</i> prenylated proteins required for endocytic trafficking and rhoptry protein sorting" @default.
- W4385620996 cites W145265700 @default.
- W4385620996 cites W1527765993 @default.
- W4385620996 cites W1583083824 @default.
- W4385620996 cites W1949622181 @default.
- W4385620996 cites W1963051611 @default.
- W4385620996 cites W1963573377 @default.
- W4385620996 cites W1969766619 @default.
- W4385620996 cites W1973638222 @default.
- W4385620996 cites W1977332101 @default.
- W4385620996 cites W1979381113 @default.
- W4385620996 cites W1983686919 @default.
- W4385620996 cites W1984470749 @default.
- W4385620996 cites W1989587437 @default.
- W4385620996 cites W1989745657 @default.
- W4385620996 cites W1991867987 @default.
- W4385620996 cites W1999345773 @default.
- W4385620996 cites W1999362171 @default.
- W4385620996 cites W1999553050 @default.
- W4385620996 cites W2002289928 @default.
- W4385620996 cites W2007558655 @default.
- W4385620996 cites W2007647318 @default.
- W4385620996 cites W2010297881 @default.
- W4385620996 cites W2020659512 @default.
- W4385620996 cites W2020872725 @default.
- W4385620996 cites W2027004293 @default.
- W4385620996 cites W2027452145 @default.
- W4385620996 cites W2028211975 @default.
- W4385620996 cites W2031521449 @default.
- W4385620996 cites W2033725939 @default.
- W4385620996 cites W2035331592 @default.
- W4385620996 cites W2040065157 @default.
- W4385620996 cites W2047045571 @default.
- W4385620996 cites W2048428839 @default.
- W4385620996 cites W2059646159 @default.
- W4385620996 cites W2062380763 @default.
- W4385620996 cites W2069184973 @default.
- W4385620996 cites W2077231529 @default.
- W4385620996 cites W2077908170 @default.
- W4385620996 cites W2080903262 @default.
- W4385620996 cites W2083656092 @default.
- W4385620996 cites W2084281420 @default.
- W4385620996 cites W2093659798 @default.
- W4385620996 cites W2097808534 @default.
- W4385620996 cites W2101898282 @default.
- W4385620996 cites W2101929642 @default.
- W4385620996 cites W2112921524 @default.
- W4385620996 cites W2116864669 @default.
- W4385620996 cites W2123382925 @default.
- W4385620996 cites W2125865922 @default.
- W4385620996 cites W2126241927 @default.
- W4385620996 cites W2127541394 @default.
- W4385620996 cites W2128378359 @default.
- W4385620996 cites W2132297897 @default.
- W4385620996 cites W2133811920 @default.
- W4385620996 cites W2139307727 @default.
- W4385620996 cites W2142248826 @default.
- W4385620996 cites W2143687466 @default.
- W4385620996 cites W2149177779 @default.
- W4385620996 cites W2153155751 @default.
- W4385620996 cites W2157060547 @default.
- W4385620996 cites W2157331313 @default.
- W4385620996 cites W2167969349 @default.
- W4385620996 cites W2168989177 @default.
- W4385620996 cites W2172177549 @default.
- W4385620996 cites W2236184415 @default.
- W4385620996 cites W2273778813 @default.
- W4385620996 cites W2312836697 @default.
- W4385620996 cites W2332204400 @default.
- W4385620996 cites W2511428910 @default.
- W4385620996 cites W2559831276 @default.
- W4385620996 cites W2566919516 @default.
- W4385620996 cites W2596280611 @default.
- W4385620996 cites W2610893454 @default.
- W4385620996 cites W2611613282 @default.
- W4385620996 cites W2751550329 @default.
- W4385620996 cites W2774464499 @default.
- W4385620996 cites W2789513868 @default.
- W4385620996 cites W2789672216 @default.