Evidence map›Paper›PMID 30905605›Full record

ArticleCurrent biology : CB2019

Acute Inhibition of Heterotrimeric Kinesin-2 Function Reveals Mechanisms of Intraflagellar Transport in Mammalian Cilia.

Martin F Engelke, Bridget Waas, Sarah E Kearns, Ayana Suber, Allison Boss, Benjamin L Allen, Kristen J Verhey

Open access · bronzeAbstract read
In one paragraph

Article in Current biology : CB, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
7.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

49 citing papers in PubMed, 77 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Disruption of primary ciliary prostaglandin EJournal of biomedical science · 2026
    Article
  7. Article
  8. Taking Down the Primary Cilium: Pathways for Disassembly in Differentiating Cells.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  9. Regulation of kinesin-2 motility by its β-hairpin motif.Nature structural & molecular biology · 2025
    Article
  10. Cholangiocytes' primary cilia regulate DNA damage response and repair.American journal of physiology. Gastrointestinal and liver physiology · 2025
    Article
  11. Article
  12. Review
  13. Article
  14. The intraflagellar transport cycle.Nature reviews. Molecular cell biology · 2025
    Review
  15. Permanent cilia loss during cerebellar granule cell neurogenesis involves withdrawal of cilia maintenance and centriole capping.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Martin F EngelkeDepartment of Cell & Developmental Biology, University of Michigan Medical School, 109 Zina Pitcher Place, Ann Arbor, MI 48109, USA. Electronic address: engelkem@med.umich.edu.
Bridget WaasDepartment of Cell & Developmental Biology, University of Michigan Medical School, 109 Zina Pitcher Place, Ann Arbor, MI 48109, USA.
Sarah E KearnsDepartment of Cell & Developmental Biology, University of Michigan Medical School, 109 Zina Pitcher Place, Ann Arbor, MI 48109, USA; Program in Chemical Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Ayana SuberDepartment of Cell & Developmental Biology, University of Michigan Medical School, 109 Zina Pitcher Place, Ann Arbor, MI 48109, USA.
Allison BossDepartment of Cell & Developmental Biology, University of Michigan Medical School, 109 Zina Pitcher Place, Ann Arbor, MI 48109, USA.
Benjamin L AllenDepartment of Cell & Developmental Biology, University of Michigan Medical School, 109 Zina Pitcher Place, Ann Arbor, MI 48109, USA.
Kristen J VerheyDepartment of Cell & Developmental Biology, University of Michigan Medical School, 109 Zina Pitcher Place, Ann Arbor, MI 48109, USA. Electronic address: kjverhey@umich.edu.
University of Michigan–Ann Arbor · US

Funding

Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3M
Kinesin Motors and Microtubule-based TraffickingR35GM131744 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Kristen J. Verhey · 2019 to 2026
$6.3M
University of Michigan Postbaccalaureate Research Education Program (UM PREP)R25GM086262 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALLEN, BENJAMIN · 2009 to 2024
$6.1M
Super-resolution Microscopy Study of Molecular Transport MechanismsR35GM122552 · NIGMS · TEMPLE UNIV OF THE COMMONWEALTH · PI Weidong Yang · 2017 to 2026
$4.5M
Hedgehog signaling in maintaining taste organ structure and function: basic and clinical studiesR01DC014428 · NIDCD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALLEN, BENJAMIN, BRADLEY, ROBERT M · 2015 to 2019
$3.3M
Cellular Biotechnology Training Program (CBTP) - Years 31-35T32GM145304 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Guizhi Zhu · 2022 to 2026
$2.6M
Structure and Function of the Ciliary Pore ComplexR01GM116204 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI VERHEY, KRISTEN J., YANG, WEIDONG · 2015 to 2018
$2.1M
Dosage-Dependent Hedgehog Signaling in Pancreatic CancerR01CA198074 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALLEN, BENJAMIN, PASCA DI MAGLIANO, MARINA · 2015 to 2019
$1.9M
Kinesin-2 Regulation of GLI Function in Hedgehog Signal TransductionR01GM118751 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALLEN, BENJAMIN · 2016 to 2019
$1.3M
NCI NIH HHS R01 CA198074NIDCD NIH HHS R01 DC014428NIDDK NIH HHS P30 DK020572NIGMS NIH HHS R01 GM116204NIGMS NIH HHS R01 GM118751NIGMS NIH HHS R25 GM086262NIGMS NIH HHS R35 GM122552NIGMS NIH HHS R35 GM131744NIGMS NIH HHS T32 GM145304
6 · The paper itself

Abstract

The trafficking of components within cilia, called intraflagellar transport (IFT), is powered by kinesin-2 and dynein-2 motors. Loss of function in any subunit of the heterotrimeric KIF3A/KIF3B/KAP kinesin-2 motor prevents ciliogenesis in mammalian cells and has hindered an understanding of how kinesin-2 motors function in cilium assembly and IFT. We used a chemical-genetic approach to generate an inhibitable KIF3A/KIF3B/KAP kinesin-2 motor (i3A/i3B) that is capable of rescuing wild-type (WT) motor function for cilium assembly and Hedgehog signaling in Kif3a/Kif3b double-knockout cells. We demonstrate that KIF3A/KIF3B function is required not just for cilium assembly but also for cilium maintenance, as inhibition of i3A/i3B blocks IFT within 2 min and leads to a complete loss of primary cilia within 8 h. In contrast, inhibition of dynein-2 has no effect on cilium maintenance within the same time frame. The kinetics of cilia loss indicate that two processes contribute to ciliary disassembly in response to cessation of anterograde IFT: a slow shortening that is steady over time and a rapid deciliation that occurs with stochastic onset. We also demonstrate that the kinesin-2 family members KIF3A/KIF3C and KIF17 cannot rescue ciliogenesis in Kif3a/Kif3b double-knockout cells or delay the loss of assembled cilia upon i3A/i3B inhibition. These results demonstrate that KIF3A/KIF3B/KAP is the sole and essential motor for cilium assembly and maintenance in mammalian cells. These findings highlight differences in how kinesin-2 motors were adapted for cilium assembly and IFT function across species.

Indexed as

Amino Acid SequenceAnimalsCiliaFlagellaKinesinsMiceNIH 3T3 CellsProtein TransportKinesinsciliaHedgehog signalinginhibitable kinesinintraflagellar transportKIF17KIF3A/KIF3B/KAPkinesin-2kinesin inhibitionprimary ciliumprotein engineering

Identifiers

PMID30905605
PMCPMC6445692
OpenAlexW2951144386

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.