Figure 6.

Open questions about the intracellular processing of Borrelia. (1) The functions of the ER-phagosome contact sites during phagosome compaction and maturation are still unknown. Likely functions concern Ca²⁺⁻ signaling, lipid transfer and regulation of trafficking. (2) The relevance of phagosome compaction for further phagolysosome maturation has been documented. However, the molecular basis for this requirement is unclear. (3) While some regulators of compaction have been identified, their individual or combined depletion leads to only a 50% reduction of compaction, indicating the likely involvement of alternative pathways. (4) Compaction is accompanied by the extrusion and abscission of membrane tubules; however, the underlying molecular mechanisms are unclear. (5) A subpopulation (1–5%) of Borrelia lose the phagosomal membrane and retain their elongated morphology. The mechanisms for this process, and its potential importance for survival in the host, are unclear. (6) The phagosome is contacted by Rab5a/SNX3 and galectin-9/flotillin-2 vesicles. Involvement of other regulatory cargo proteins and lipids, along with further vesicle populations, is likely but unproven. (7) The interaction between vesicles and the phagosomal membrane likely happens in a “kiss-and-run” fashion. The molecular mechanisms are unknown. (8) The degradative machinery is well described for other phagocytic targets. However, it is unknown whether the same enzymes, such as cathepsins and NOX-2, are also involved in proteolytic processing of Borrelia.