Phospho-regulation accommodates Type III secretion and assembly of a tether of ER- Chlamydia inclusion membrane contact sites

Rebecca L. Murray, Rachel J. Ende, Samantha K. D’Spain, Isabelle Derré
2021 · doi:10.1101/2021.10.19.465067
preprint OA: closed CC-BY-4.0
📄 Open PDF View at publisher

Abstract

Membrane contact sites (MCS) are crucial for non-vesicular trafficking-based inter-organelle communication. ER-organelle tethering occurs in part through the interaction of the ER resident protein VAP with FFAT-motif containing proteins. FFAT motifs are characterized by a seven amino acidic core surrounded by acid tracks. We have previously shown that the human intracellular bacterial pathogen Chlamydia trachomatis establishes MCS between its vacuole (the inclusion) and the ER through expression of a bacterial tether, IncV, displaying molecular mimicry of eukaryotic FFAT motif cores. Here, we show that multiple layers of host cell kinase-mediated phosphorylation events govern the assembly of the IncV-VAP tethering complex. CK2-mediated phosphorylation of a C-terminal region of IncV enables IncV hyperphosphorylation of a phospho- FFAT motif core and serine-rich tracts immediately upstream of IncV FFAT motif cores. Phosphorylatable serine tracts, rather than genetically-encoded acidic tracts, accommodate Type III-mediated translocation of IncV to the inclusion membrane, while achieving full mimicry of FFAT motifs. Thus, regulatory components and post-translational modifications are integral to MCS biology, and intracellular pathogens such as C. trachomatis have evolved complex molecular mimicry of these eukaryotic features.

My notes (saved in your browser only)

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. The paper's references may be in our DB but unresolved to ``paper_id`` (resolution happens at ingest when the cited DOI matches a row we already have). Run the cross-source citation reconcile pass to retry.

References (37)

Source provenance

crossref
last seen: 2026-07-24T06:58:22.734854+00:00
europepmc
last seen: 2026-05-19T01:45:01.086888+00:00
unpaywall
last seen: 2026-05-22T02:00:06.705733+00:00
License: CC-BY-4.0