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Open research questions in Cellular transport and secretion

54 unresolved questions extracted from the limitations and future-work sections of 217 Cellular transport and secretion papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • TANGO1, encoded by MIA3, organizes ER exit sites for bulky cargo export, yet the molecular basis of cargo recognition and its relationship to the collagen-specific chaperone HSP47 remain unclear.

    A conserved cargo recognition mechanism establishes TANGO1 as a selective extracellular matrix cargo receptor · 2026 · DOI

  • Preventing myristoylation of ARF6 or geranylgeranylation of Rab11a strongly reduced recruitment, whereas prenylation alone was insufficient, indicating recognition of a composite membrane-targeting code.

    Lipid Imbalance Generates Golgi Whorls that Sequester Small GTPases · 2026 · DOI

  • How Epstein-Barr virus (EBV) overcomes the spatial constraints imposed by the narrow perinuclear space for nuclear egress of the viral capsids remains unclear.

    Epstein Barr virus exploits ER stress and TMX4 dependent nuclear envelope remodeling to enable capsid egress · 2026 · DOI

  • However, in cell and model membranes, Syntaxin and SNAP25 are known to oligomerize and cluster, and little is known about how clustering affects their incorporation into SNARE complexes.

    Munc18 binds to and organizes membrane-bound acceptor Q-SNARE complexes in a fashion that depends on the membrane's lipid composition · 2026 · DOI

  • CLIMP-63 has been proposed to be the principal determinant of this spacing, but the molecular mechanism by which it controls luminal width remains unclear.

    The luminal and cytosolic domains of CLIMP-63 cooperate to set ER sheet width · 2026 · DOI

  • Despite evidence that annexin and endosomal sorting complex required for transport (ESCRT) proteins are required for PM repair, the extent to which their recruitment is coordinated at sites of membrane damage remains unclear.

    Sorcin couples Annexin A11 recruitment to ESCRT-III assembly for plasma membrane repair · 2026 · DOI

  • The Endosomal Sorting Complexes Required for Transport (ESCRT) pathway governs multivesicular body (MVB) formation, lysosomal cargo delivery, and autophagosome closure, yet its expression profile in human MND tissue and mechanistic contribution to disease pathology have not been established.

    ESCRT Machinery Dysfunction in Motor Neurone Disease: TSG101, CHMP2B, and VPS4a Differentially Regulate TDP-43 Pathology, Autophagy, and Exosome Biogenesis · 2026 · DOI

  • The binding sites for Gq on PLC{beta} are well-established and much has been learned about its mechanism of activation, but comparatively little is known about G{beta}{gamma}-dependent activation.

    Gβγ engages PLCβ3 at multiple sites to reorient and facilitate its activation · 2026 · DOI

  • Significance StatementSynaptic plasticity relies on dynamic trafficking and turnover of membrane proteins, including AMPA-type glutamate receptors (AMPARs), yet how receptor trafficking intersects with ubiquitin-mediated sorting pathways at synapses remains unclear.

    ESCRT-0 regulates AMPA receptor currents and Ca2+- dependent signaling · 2026 · DOI

  • The ESCRT (endosomal sorting complexes required for transport) machinery binds and sorts ubiquitinated membrane proteins into lysosomes for degradation, yet the presence and function of ESCRTs in sorting ubiquitinated AMPA and other receptors at the post-synapse remain unclear.

    ESCRT-0 regulates AMPA receptor currents and Ca2+- dependent signaling · 2026 · DOI

  • Several sorting nexin (Snx) proteins have established roles in the endosomal network, but the function of many members of this phospholipid‐binding protein family such as Snx21 is still poorly investigated.

    The sorting nexin Snx21 promotes flotillin‐mediated endocytosis · 2026 · DOI

  • NECAP proteins physically bind phosphorylated AP-2 during CME, but their roles during endocytosis remain unresolved, with conflicting reports about their function.

    NECAP antagonizes light-induced Rhodopsin-1 internalization to promote photoreceptor homeostasis · 2026 · DOI

  • How broadly expressed presynaptic proteins acquire the cell-type specificity needed to couple to CaV2 channels in defined neurons, and whether this specialization contributes to behavior, remains poorly understood.

    Nociceptor-enriched CAPS1 isoform couples to CaV2.2 channels and underlies inflammatory pain hypersensitivity · 2026 · DOI

  • While the J-domain protein RME-8/DNAJC13 is known to maintain these boundaries by actively removing degradative machinery from the recycling microdomain, other factors that contribute to this spatial organization remain poorly defined.

    SCM-1/SCAMP Maintains Microdomain Boundaries and Cargo Sorting within the Endosomal System · 2026 · DOI

  • While retinal pigment epithelial (RPE) cells remove shed outer segment tips through daily phagocytosis, the mechanisms by which photoreceptors eliminate misfolded or mistargeted proteins are not well understood.

    PIKfyve preserves endolysosomal function in photoreceptors and RPE cells to maintain retinal integrity · 2026 · DOI

  • Moreover, PCP protein complexes are located at adherens junctions and their polarization requires the activity of non-muscle myosin II (NMII), but how NMII contributes to PCP is not fully understood.

    Myosin-dependent partitioning of junctional Prickle2 toward the anterior vertex during planar polarization of Xenopus neuroectoderm · 2026 · DOI

  • Missense mutations in the Grik2 gene that encodes the kainate receptor subunit GluK2 are associated with neurodevelopmental disorders, but how individual mutations perturb receptor regulation remains unclear.

    Disease-associated mutations in GluK2 disrupt compartment-specific regulatory mechanisms controlling kainate receptor membrane trafficking. · 2026 · DOI

  • ABSTRACT Clathrin‐mediated endocytosis (CME) is vital to plant physiology; however, the molecular details of how it functions in these complex multicellular eukaryotes remain to be defined relative to model yeast and animal systems.

    Clathrin‐Mediated Endocytosis in Plants: Historical to Modern Advances · 2026 · DOI

  • Although the molecular machinery of STING activation is extensively studied and defined, the one underlying STING degradation and inactivation has not yet been fully elucidated.

    STING signalling is terminated through ESCRT-dependent microautophagy of vesicles originating from recycling endosomes · 2023 · DOI

  • The study uses siRNA knockdown of CHMP2A to show differential repair of small versus large membrane disruptions, but the specific size threshold or biophysical parameters that determine whether disruptions are repaired by ESCRT-III-mediated shedding versus patching-based mechanisms has not been quantitatively characterized.

    Cell Biology: ESCRTing Trouble Out! · 2014 · DOI

  • Calcium regulation is demonstrated for ESCRT-mediated membrane repair at the plasma membrane, but whether this calcium signaling pathway generalizes to other ESCRT-dependent vesicle formation events such as multivesicular body biogenesis or retroviral budding requires comparative mechanistic analysis.

    Cell Biology: ESCRTing Trouble Out! · 2014 · DOI

  • The paper demonstrates ESCRT-mediated ectsome shedding at artificial laser-induced membrane disruptions under controlled culture conditions, but whether this pathway functions as a physiologically important mechanism for ectosome production during naturally-occurring membrane disruptions in vivo has not been established.

    Cell Biology: ESCRTing Trouble Out! · 2014 · DOI

  • ALIX is identified as a calcium-binding protein capable of recruiting ESCRT-III components in the absence of ESCRT-I/II, but whether other non-ESCRT proteins besides ALIX participate in ESCRT-III recruitment at membrane disruption sites has not been investigated.

    Cell Biology: ESCRTing Trouble Out! · 2014 · DOI

  • Previous work showed that pore-formation-induced budding by streptolysin O occurred in fixed cells (suggesting mechanical rather than protein-mediated budding), yet only the final scission event was calcium-dependent; experiments are needed to determine whether ESCRT-III proteins function exclusively in the scission step rather than the budding step of membrane repair.

    Cell Biology: ESCRTing Trouble Out! · 2014 · DOI

  • The study demonstrates ESCRT-III-mediated repair of small laser-induced membrane disruptions through CHMP2A knockdown, but the mechanism by which outward budding occurs in the absence of ESCRT-I/II complexes—proteins typically required for ESCRT-mediated membrane budding—remains uncharacterized and needs mechanistic analysis.

    Cell Biology: ESCRTing Trouble Out! · 2014 · DOI

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54 open questions have been extracted from the limitations and future-work passages of 217 Cellular transport and secretion papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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