Paul Conduit

Paul Conduit

@pconduit.bsky.social

Biologist and sports fan

310 followers121 following14 posts

Paul Conduit
@pconduit.bsky.social

CAI is absent from human proteins, where a conserved SCC-LCC CM1 hairpin that blocks one of the key F residues is sufficient for autoinhibition. In contrast, this hairpin is necessary for CM1 binding in Drosophila Cnn, explaining the requirement for CAI domain-mediated autoinhibition.

Paul Conduit
@pconduit.bsky.social

In summary, we provide the first structural model for CM1 autoinhibition, a key mechanism that helps spatially regulate #microtubule nucleation. We also highlight key evolutionary differences in CM1 binding mechanisms.

Paul Conduit
@pconduit.bsky.social

We previously showed that an upstream CM1 autoinhibition domain is required to prevent binding and activation of g-TuRCs by #Drosophila Centrosomin (Cnn) to avoid ectopic cytosolic #microtubule nucleation and major #cell and #developmental defects rupress.org/jcb/article/...

rupress.orgAutoinhibition of Cnn binding to γ-TuRCs prevents ectopic microtubule nucleation and cell division defectsWe show that autoinhibition regulates the binding between microtubule nucleating complexes and proteins that tether them to sites of microtubule nucleation
Paul Conduit
@pconduit.bsky.social

In this latest paper, we show that the CAI domain forms a 4-helix dimer that associates with the short coiled-coil (SCC) part of the CM1 domain (equivalent of g-TuNA in humans), blocking the otherwise exposed key phenylalanine (F115) residue required for g-TuRC binding.

Paul Conduit reposted

Nikos Konstantinides
@nkonst4.bsky.social

I am very happy (and a bit scared) to present to you what we have been working on over the last 4 years. This manuscript is exactly what I dreamt of when I started the lab and I could not be happier and prouder of the outcome!

bioRxivpreprint@biorxivpreprint.bsky.social

Evolutionary dynamics of temporal transcription factor series in the insect optic lobe https://www.biorxiv.org/content/10.64898/2026.01.08.698497v1

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Paul Conduit
@pconduit.bsky.social

Depleting CLASP or reducing the levels of g-TuRC at the Golgi perturb asymmetric microtubule nucleation towards the axon, causing more MT plus ends to grow towards and into dendrites (on the opposite side of the soma). This perturbs dendritic MT polarity, which is normally mainly minus-end-out.

Paul Conduit
@pconduit.bsky.social

We propose that the plus ends of MTs nucleated by g-TuRCs at the cis-Golgi are stabilised by CLASP at the trans-Golgi such that MTs grow along the cis-to-trans Golgi axis and thus grow towards and into axons rather than dendrites. This mechanism therefore helps maintain MT polarity in neurons.

Paul Conduit
@pconduit.bsky.social

In neurons, MTs in axons have their plus ends pointing away from the soma (plus-end-out) while many MTs in dendrites have their plus ends pointing towards the soma (minus-end-out). This differential polarity is important for correct cargo sorting, neurite identity, neuronal development and function

Paul Conduit
@pconduit.bsky.social

We show that specific Golgi stacks within the soma are oriented cis-to-trans towards the axon entry site and that these Golgi stacks nucleate MTs towards the axon. We find that MT nucleating g-TuRCs and MT plus-end stabilising CLASP localise to the cis- and trans- Golgi compartments respectively.

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