The data presented in this study shed light on the involvement of all the known five autophagy cargo receptors (also known as autophagy adaptors) i.e. SQSTM1, NDP52, OPTN, NBR1 and TAX1BP1, in mediating the restriction of the intracellular growth of L. monocytogenes. The involvement of the three autophagy adaptors: OPTN, NBR1 and TAX1BP1, previously unknown to link L. monocytogenes to the autophagosomal membrane, has been identified. The phosphorylation of OPTN by TBK1 was essential for the growth restriction of L. monocytogenes. NBR1 seems to be the most important autophagy cargo receptor for L. monocytogenes, as it was the only one to restrict the growth of both Lm EGD-e and Lm?actA2. NBR1 knockdown also resulted in the highest increase in the intracellular growth of Lm EGD-e (2.9-fold) and Lm?actA2 (1.9-fold), as compared to the other cargo receptors. With the exception of NBR1, the absence of all the other autophagy cargo receptors: OPTN, SQSTM1, NDP52 and TAX1BP1, only led to increased intracellular loads of Lm EGD-e, but not those of Lm?actA2. Because of its inability to move within the host cell cytosol after its escape from the phagosomal compartment, Lm?actA is much more ubiquitinated than Lm EGD-e. This may lead to the simultaneous binding of several autophagy cargo receptors to Lm?actA, thereby linking it to the autophagosomal membrane for its subsequent degradation. Lm EGD-e, on the other hand, is capable of intracellular movement by means of the ActA protein. It is, therefore, susceptible to autophagy at different stages, like at the time of multiplication in the cytoplasm, or while entering from one cell to the other, and all the five known autophagy adaptors are capable of recruiting it to the autophagosome. A part of the population of Lm EGD-e that is free in the cytoplasm is targeted by autophagy, while another part of this population forms an actin tail and moves from one cell to the other.
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