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Open research questions in Microtubule and mitosis dynamics

60 unresolved questions extracted from the limitations and future-work sections of 207 Microtubule and mitosis dynamics papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Although loss of KIFBP has been linked to reduced neurite length and microtubule disorganization, the specific kinesins underlying these phenotypes remain unclear.

    A systems-level proteomic analysis identifies kinesin targets of KIFBP during neuronal development · 2026 · DOI

  • The polymerase and binding measurements can be unified within the biochemical model: Stu2 operates with high efficiency, acting as a tubulin-shuttling antenna on the microtubule end that is primarily limited by the rate of tubulin:TOG association.

    A biochemical mechanism for Stu2/XMAP215-family microtubule polymerases · 2026 · DOI

  • Stu2/XMAP215-family polymerases use tubulin-binding TOG domains to catalyze microtubule growth, but how polymerase activity results from the number and tubulinbinding properties of TOGs is not understood.

    A biochemical mechanism for Stu2/XMAP215-family microtubule polymerases · 2026 · DOI

  • The mechanistic basis for why only a subset of mouse zygotene spermatocytes forms primary cilia remains unclear, particularly when contrasted with zebrafish oocytes, where the majority of zygotene cells are ciliated (Mytlis et al, 2022). Although the role of sperm flagella in driving motility and fertilization is well established, the biological significance of zygotene cilia in the testis is not yet understood.

    Basal body docking failure triggers centriole clustering and elimination in mammalian spermatogenesis · 2026 · DOI

  • Nuclear distribution element 1 (NDE1) is a centrosome-associated regulator of dynein-dependent processes and ciliogenesis, but its nanoscale organization and contribution to centrosome architecture remain incompletely understood.

    NDE1 Localizes to the Subdistal Appendages to Maintain Centrosome Integrity and Microtubule Organization · 2026 · DOI

  • Biogenesis of the centrin arm requires the Polo-like kinase homolog TbPLK and the orphan kinesin KIN-G, but the mechanistic role of TbPLK in centrin arm biogenesis remains elusive.

    Polo-like kinase phosphorylation of the orphan kinesin KIN-G negatively regulates centrin arm biogenesis in Trypanosoma brucei · 2026 · DOI

  • The kinetochore is a complex multi-protein machine comprising more than 40 distinct proteins, but the functional roles of many components remain unclear.

    An interdependent Cbf1-CCAN interaction stabilizes the budding yeast kinetochore · 2026 · DOI

  • Angstrom-scale changes in microtubule (MT) lattice spacing regulate the selective recruitment of MT-associated proteins, yet how these structural states operate in cells remains poorly understood.

    Curved microtubule regions mark sites of lattice compaction in cells and neurons · 2026 · DOI

  • In human cells, the Ska and Ndc80 complexes (SkaC and Ndc80C) cooperate to sustain these attachments, but how they are organized on microtubules and coupled to end dynamics remains unclear.

    Structural Basis of Human Kinetochore-Microtubule Coupling by the Ndc80 and Ska Complexes · 2026 · DOI

  • In contrast, an Ect2 variant that was lacking constitutive plasma membrane association via the polybasic cluster, was not only incapable of pulse suppression but instead even stimulated strong pulsatile Rho dynamics.

    Constitutive plasma membrane interaction of active Rho GEF Ect2 inhibits cortex contraction pulses · 2026 · DOI

  • Here, we mimicked this mitotic state by expressing a constitutively active Ect2 variant that is lacking its nuclear localization signal in interphase, to examine its interplay with Lbc-stimulated pulsatile Rho dynamics.

    Constitutive plasma membrane interaction of active Rho GEF Ect2 inhibits cortex contraction pulses · 2026 · DOI

  • Radial glial cells (RGCs) generate cortical neurons and guide radial neuronal migration, yet how microtubule (MT) regulators coordinate progenitor maintenance, mitotic fidelity, and cortical architecture remains unclear.

    Kif2C safeguards radial glial integrity to prevent cortical malformation · 2026 · DOI

  • Although KANK proteins link talin-containing FAs to cortical MT-capture machinery, how this machinery couples to force-bearing actin networks remains unclear.

    CCDC66 couples actin-microtubule crosslinking to KANK1-associated microtubule targeting and focal adhesion turnover · 2026 · DOI

  • Although our data demonstrate that CKAP2L interacts with AKT and sustains PI3K/AKT signaling by suppressing ubiquitin- proteasome-mediated AKT degradation, it remains unclear whether CKAP2L directly inhibits AKT ubiquitination or indirectly regu- lates this process by recruiting specific E3 ligases or deubiquitinases. Moreover, although our findings suggest that CKAP2L contributes to F-actin cytoskel- eton remodeling in EC cells, the precise mechanisms by which CKAP2L coordinates microtubule dynamics and actin cytoskeleton organization remain to be elucidated.

    CKAP2L promotes endometrial cancer progression by suppressing AKT ubiquitination and activating the PI3K/AKT signaling pathway · 2026 · DOI

  • The peroxisome motility assay is described with specific conditions (37°C, 5% CO2, 6 consecutive 3-min movies), but the text does not discuss whether these parameters have been validated across different cell types or experimental conditions.

    PACS1 syndrome mutation disrupts dynein-mediated cargo transport via HDAC6 and BICD2 · 2026 · DOI

  • The LC-MS/MS analysis uses a Human UniProt database from March 2019; updating to more recent protein databases could potentially identify additional interacting partners not captured in the original analysis.

    PACS1 syndrome mutation disrupts dynein-mediated cargo transport via HDAC6 and BICD2 · 2026 · DOI

  • The sucrose gradient fractionation protocol compares only one patient (159) and one healthy control (160); larger sample sizes would be needed to establish whether observed differences are generalizable across PACS1 syndrome patients.

    PACS1 syndrome mutation disrupts dynein-mediated cargo transport via HDAC6 and BICD2 · 2026 · DOI

  • While confocal microscopy analyses of Golgi localization are described, the text does not address potential limitations in automated thresholding or ROI definition across different cell types with varying morphologies.

    PACS1 syndrome mutation disrupts dynein-mediated cargo transport via HDAC6 and BICD2 · 2026 · DOI

  • The excerpt presents detailed methodological descriptions but does not explicitly discuss limitations of the IP approach, such as potential false positives from overexpression artifacts or the specificity of the antibodies used.

    PACS1 syndrome mutation disrupts dynein-mediated cargo transport via HDAC6 and BICD2 · 2026 · DOI

  • However, how dynein and dynactin recognize diverse adaptors, how they interact with each other during complex formation, and the role of critical regulators such as lissencephaly-1 (LIS1) protein (LIS1) remain unclear.

    Molecular mechanism of dynein-dynactin complex assembly by LIS1 · 2024 · DOI

  • The hypothesis that direct Centralspindlin–ALIX binding without CEP55 represents the ancestral ESCRT recruitment mechanism during cytokinesis has only been tested in Drosophila. This hypothesis requires experimental validation in other invertebrate model organisms, particularly C. elegans, to establish evolutionary conservation and mechanistic principles across species.

    Cell Biology: Alix ESCRTs Pavarotti during Cell Division · 2019 · DOI

  • The apparent discrepancy in cultured mammalian cell lines where ALIX is lost from the midbody after CEP55 depletion while MKLP1/MKLP2 remain correctly localized has not been explained. Investigation is needed to determine whether MKLP1-mediated ALIX recruitment functions only in specific cell types with low CEP55 expression and how this relates to MKLP1's direct interaction with ESCRT-III protein CHMP4C.

    Cell Biology: Alix ESCRTs Pavarotti during Cell Division · 2019 · DOI

  • Direct binding between ALIX and kinesin-6 family proteins (Subito in Drosophila, ZEN-4 in C. elegans, MKLP1 and MKLP2 in mammals) via the LxxIF motif has not been experimentally validated. This alternative ESCRT recruitment mechanism must be tested biochemically to determine whether these kinesins can substitute for CEP55-mediated ALIX recruitment at the midbody.

    Cell Biology: Alix ESCRTs Pavarotti during Cell Division · 2019 · DOI

  • The functional significance of the evolutionary transition from the simple Pavarotti–Alix–Tsg101–ESCRT complex in invertebrates to the more complex MKLP1–CEP55–ALIX–TSG101–ESCRT complex in vertebrates during cytokinesis has not been determined. Whether CEP55's microtubule-bundling activity provides a selective advantage for successful abscission in vertebrates requires functional characterization.

    Cell Biology: Alix ESCRTs Pavarotti during Cell Division · 2019 · DOI

  • The regulation of Alix–Tsg101 interaction with Pavarotti in Drosophila cells, which lack CEP55, remains uncharacterized. The authors propose that direct phosphorylation of Alix, Tsg101, and/or Pavarotti by Plk1 or other mitotic kinases may control this interaction, but this hypothesis has not been experimentally tested.

    Cell Biology: Alix ESCRTs Pavarotti during Cell Division · 2019 · DOI

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60 open questions have been extracted from the limitations and future-work passages of 207 Microtubule and mitosis dynamics 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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