Proteomics

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Extensive structural rearrangement of intraflagellar transport trains underpins bidirectional cargo transport (Proteomics


ABSTRACT: Bidirectional transport in cilia is carried out by polymers of the IFTA and IFTB protein complexes, referred to as anterograde and retrograde IFT “trains”. Anterograde trains deliver cargoes from the cell to the ciliary tip, then remodel into retrograde trains for cargo export. We set out to understand how the structure of these trains changes at the tip, and thus how the same IFT complexes can perform opposing transport roles. We use cryo-electron tomography, subtomogram averaging and in-situ cross-linking mass spectrometry to determine the structure of retrograde IFT trains, and compare with the known anterograde train structure. We show that the retrograde train is a two-fold symmetric polymer organised around a central thread of IFTA complexes. We conclude that the structural differences between anterograde and retrograde trains can only be achieved through de novo polymerisation of the retrograde train from individual IFTA/B complexes. Finally we describe how conformational changes to cargo binding sites allow for unidirectional cargo transport in a bidirectional system.

ORGANISM(S): Chlamydomonas Reinhardtii

SUBMITTER: Gaia Pigino 

PROVIDER: PXD049260 | JPOST Repository | Wed Aug 21 00:00:00 BST 2024

REPOSITORIES: jPOST

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Publications

Extensive structural rearrangement of intraflagellar transport trains underpins bidirectional cargo transport.

Lacey Samuel E SE   Graziadei Andrea A   Pigino Gaia G  

Cell 20240726 17


Bidirectional transport in cilia is carried out by polymers of the IFTA and IFTB protein complexes, called anterograde and retrograde intraflagellar transport (IFT) trains. Anterograde trains deliver cargoes from the cell to the cilium tip, then convert into retrograde trains for cargo export. We set out to understand how the IFT complexes can perform these two directly opposing roles before and after conversion. We use cryoelectron tomography and in situ cross-linking mass spectrometry to deter  ...[more]

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