Working model of Tex2 functions at ER–LE/lys MCSs. (A) Functional dissection of Tex2. Tex2-NT (1-517) containing essential residues 1-277 is required for binding the catalytic motif CX5R of TMEM55. The residues 278-514 is required for targeting Tex2 to tubular ER. The SMP domain is likely responsible for transferring glycerophospholipids and sphingolipids between the ER and LE/lys. The PH domain of Tex2 may be involved in the regulation of Tex2–TMEM55 interactions. (B) Tex2 resides exclusively on tubular ER, is recruited to ER–LE/lys MCSs via LE/lys-resident PI phosphatases TMEM55. The Tex2–TMEM55 interaction is negatively regulated by PI4KII activities. The loss of Tex2 at these contacts resulted in defects in lysosomal digestive functions and impaired autophagic flow, possibly due to the defective lipid composition of LE/lys membranes.
