Multiple interactions of the dynein-2 complex with the IFT-B complex are required for effective intraflagellar transport

Asante, D., Stevenson, N. L. and Stephens, D. J. (2014). Subunit composition of

the human cytoplasmic dynein-2 complex. J. Cell Sci. 127, 4774-4787. doi:10.

1242/jcs.159038

Badgandi, H. B., Hwang, S., Shimada, I. S., Loriot, E. and Mukhopadhyay, S.

(2017). Tubby family proteins are adaptors for ciliary trafficking of integral

membrane proteins. J. Cell Biol. 216, 743-760. doi:10.1083/jcb.201607095

Braun, D. A. and Hildebrandt, F. (2017). Ciliopathies. Cold Spring Harb. Perspect.

Biol. 9, a028191. doi:10.1101/cshperspect.a028191

Brown, J. M. and Witman, G. B. (2014). Cilia and diseases. Bioscience 64,

1126-1137. doi:10.1093/biosci/biu174

De-Castro, A. R. G., Rodrigues, D. R. M., De-Castro, M. J. G., Vieira, N.,

Vieira, C., Carvalho, A. X., Gassmann, R., Abreu, C. M. C. and Dantas, T. J.

(2022). WDR60-mediated dynein-2 loading into cilia powers retrograde IFT and

transition zone crossing. J. Cell Biol. 221, e202010178. doi:10.1083/jcb.

202010178

Funabashi, T., Katoh, Y., Okazaki, M., Sugawa, M. and Nakayama, K. (2018).

Interaction of heterotrimeric kinesin-II with IFT-B-connecting tetramer is crucial for

ciliogenesis. J. Cell Biol. 217, 2867-2876. doi:10.1083/jcb.201801039

Garcia-Gonzalo, F. R. and Reiter, J. F. (2017). Open sesame: how transition fibers

and the transition zone control ciliary composition. Cold Spring Harb. Perspect.

Biol. 9, a028134. doi:10.1101/cshperspect.a028134

Hamada, Y., Tsurumi, Y., Nozaki, S., Katoh, Y. and Nakayama, K. (2018).

Interaction of WDR60 intermediate chain with TCTEX1D2 light chain of the

dynein-2 complex is crucial for ciliary protein trafficking. Mol. Biol. Cell 29,

1628-1639. doi:10.1091/mbc.E18-03-0173

Hirano, T., Katoh, Y. and Nakayama, K. (2017). Intraflagellar transport-A complex

mediates ciliary entry and retrograde trafficking of ciliary G protein-coupled

receptors. Mol. Biol. Cell 28, 429-439. doi:10.1091/mbc.e16-11-0813

Iomini, C., Babaev-Khaimov, V., Sassaroli, M. and Piperno, G. (2001). Protein

particles in Chlamydomonas flagella undergo a transport cycle consisting of four

phases. J. Cell Biol. 153, 13-24. doi:10.1083/jcb.153.1.13

Ishida, Y., Kobayashi, T., Chiba, S., Katoh, Y. and Nakayama, K. (2021).

Molecular basis of ciliary defects caused by compound heterozygous IFT144/

WDR19 mutations found in cranioectodermal dysplasia. Hum. Mol. Genet. 30,

213-225. doi:10.1093/hmg/ddab034

Jensen, V. L., Lambacher, N. J., Li, C., Mohan, S., Williams, C. L., Inglis, P. N.,

Yoder, B. K., Blacque, O. E. and Leroux, M. R. (2018). Role for intraflagellar

transport in building a functional transition zone. EMBO Rep. 19, e45862. doi:10.

15252/embr.201845862

Jordan, M. A. and Pigino, G. (2021). The structural basis of intraflagellar transport

at a glance. J. Cell Sci. 134, jcs247163. doi:10.1242/jcs.247163

Jordan, M. A., Diener, D. R., Stepanek, L. and Pigino, G. (2018). The cryo-EM

structure of intraflagellar transport trains reveals how dynein is inactivated to

ensure unidirectional anterograde movement in cilia. Nat. Cell Biol. 20,

1250-1255. doi:10.1038/s41556-018-0213-1

Katoh, Y., Nozaki, S., Hartanto, D., Miyano, R. and Nakayama, K. (2015).

Architectures of multisubunit complexes revealed by a visible immunoprecipitation

assay using fluorescent fusion proteins. J. Cell Sci. 128, 2351-2362. doi:10.1242/

jcs.168740

Katoh, Y., Terada, M., Nishijima, Y., Takei, R., Nozaki, S., Hamada, H. and

Nakayama, K. (2016). Overall architecture of the intraflagellar transport (IFT)-B

complex containing Cluap1/IFT38 as an essential component of the IFT-B

peripheral subcomplex. J. Biol. Chem. 291, 10962-10975. doi:10.1074/jbc.M116.

713883

Katoh, Y., Nakamura, K. and Nakayama, K. (2018). Visible immunoprecipitation

(VIP) assay: a simple and versatile method for visual detection of protein-protein

interactions. Bio-protocol 8, e2687. doi:10.21769/BioProtoc.2687

Katoh, Y., Chiba, S. and Nakayama, K. (2020). Practical method for

superresolution imaging of primary cilia and centrioles by expansion

microscopy using an amplibody for fluorescence signal amplification. Mol. Biol.

Cell 31, 2195-2206. doi:10.1091/mbc.E20-04-0250

Kobayashi, T., Ishida, Y., Hirano, T., Katoh, Y. and Nakayama, K. (2021).

Cooperation of the IFT-A complex with the IFT-B complex is required for ciliary

retrograde protein trafficking and GPCR import. Mol. Biol. Cell 32, 45-56. doi:10.

1091/mbc.E20-08-0556

Kopinke, D., Norris, A. M. and Mukhopadhyay, S. (2021). Developmental and

regenerative paradigms of cilia regulated hedgehog signaling. Sem. Cell Dev.

Biol. 110, 89-103. doi:10.1016/j.semcdb.2020.05.029

Kozminski, K. G., Beech, P. L. and Rosenbaum, J. L. (1995). The

Chlamydomonas kinesin-like protein FLA10 is involved in motility associated

with the flagellar membrane. J. Cell Biol. 131, 1517-1527. doi:10.1083/jcb.131.6.

1517

Journal of Cell Science (2023) 136, jcs260462. doi:10.1242/jcs.260462

Lacey, S. E., Foster, H. E. and Pigino, G. (2023). The molecular structure of IFT-A

and IFT-B in anterograde intraflagellar transport trains. Nat. Struct. Mol. Biol.

[Epub]. doi:10.1038/s41594-022-00905-5

Liu, P. and Lechtreck, K. F. (2018). The Bardet-Biedl syndrome protein complex is

an adaptor expanding the cargo of range of intraflagellar transport trains for ciliary

export. Proc. Natl. Acad. Sci. USA 115, E934-E943. doi:10.1073/pnas.

1713226115

Mcinerney-Leo, A. M., Schmidts, M., Corté s, C. R., Leo, P. J., Gener, B.,

Courtney, A. D., Gardiner, B., Harris, J. A., Lu, Y., Marshall, M. et al. (2013).

Short-rib polydactyly and Jeune syndromes are caused by mutations in WDR60.

Am. J. Hum. Genet. 93, 515-523. doi:10.1016/j.ajhg.2013.06.022

Mcinerney-Leo, A. M., Harris, J. E., Marshall, M. S., Gardiner, B., Kinning, E.,

Leong, H. Y., Mckenzie, F., Ong, W. P., Vodopiutz, J., Wicking, C. et al. (2015).

Whole exome sequencing is an efficient, sensitive and specific method for

determining the genetic cause of short-rib thoracic dystrophies. Clin. Genet. 88,

550-557. doi:10.1111/cge.12550

Mukhopadhyay, S., Wen, X., Chih, B., Nelson, C. D., Lane, W. S., Scales, S. J.

and Jackson, P. K. (2010). TULP3 bridges the IFT-A complex and membrane

phosphoinositides to promote trafficking of G protein-coupled receptors into

primary cilia. Genes Dev. 24, 2180-2193. doi:10.1101/gad.1966210

Nachury, M. V. and Mick, D. U. (2019). Establishing and regulating the composition

of cilia for signal transduction. Nat. Rev. Mol. Cell Biol. 20, 389-405. doi:10.1038/

s41580-019-0116-4

Nakamura, K., Noguchi, T., Takahara, M., Omori, Y., Furukawa, T., Katoh, Y. and

Nakayama, K. (2020). Anterograde trafficking of ciliary MAP kinase-like ICK/

CILK1 by the intraflagellar transport machinery is required for intraciliary

retrograde protein trafficking. J. Biol. Chem. 295, 13363-13376. doi:10.1074/jbc.

RA120.014142

Nakayama, K. and Katoh, Y. (2020). Architecture of the IFT ciliary trafficking

machinery and interplay between its components. Crit. Rev. Biochem. Mol. Biol.

55, 179-196. doi:10.1080/10409238.2020.1768206

Nishijima, Y., Hagiya, Y., Kubo, T., Takei, R., Katoh, Y. and Nakayama, K. (2017).

RABL2 interacts with the intraflagellar transport B complex and CEP19 and

participates in ciliary assembly. Mol. Biol. Cell 28, 1652-1666. doi:10.1091/mbc.

e17-01-0017

Nozaki, S., Katoh, Y., Terada, M., Michisaka, S., Funabashi, T., Takahashi, S.,

Kontani, K. and Nakayama, K. (2017). Regulation of ciliary retrograde protein

trafficking by the Joubert syndrome proteins ARL13B and INPP5E. J. Cell Sci.

130, 563-576. doi:10.1242/jcs.197004

Nozaki, S., Katoh, Y., Kobayashi, T. and Nakayama, K. (2018). BBS1 is involved

in retrograde trafficking of ciliary GPCRs in the context of the BBSome complex.

PLoS One 13, e0195005. doi:10.1371/journal.pone.0195005

Nozaki, S., Castro Araya, R. F., Katoh, Y. and Nakayama, K. (2019). Requirement

of IFT-B–BBSome complex interaction in export of GPR161 from cilia. Biol. Open

8, bio043786. doi:10.1242/bio.043786

Okazaki, M., Kobayashi, T., Chiba, S., Takei, R., Liang, L., Nakayama, K. and

Katoh, Y. (2020). Formation of the B9-domain protein complex MKS1–B9D2–

B9D1 is essential as a diffusion barrier for ciliary membrane proteins. Mol. Biol.

Cell 31, 2259-2268. doi:10.1091/mbc.E20-03-0208

Park, K. and Leroux, M. R. (2022). IFT trains overcome an NPHP module barrier at

the transition zone. J. Cell Biol. 221, e202112015. doi:10.1083/jcb.202112015

Pedersen, L. B., Geimer, S. and Rosenbaum, J. L. (2006). Dissecting the

molecular mechanisms of intraflagellar transport in Chlamydomonas. Curr. Biol.

16, 450-459. doi:10.1016/j.cub.2006.02.020

Perez-Riverol, Y., Bai, J., Bandla, C., Garcia-Seisdedos, D., Hewapathirana, S.,

Kamatchinathan, S., Kundu, D. J., Prakash, A., Frericks-Zipper, A.,

Eisenacher, M. et al. (2022). The PRIDE database resources in 2022: a hub

for mass spectrometry-based proteomics evidences. Nucleic Acids Res. 50,

D543-D552. doi:10.1093/nar/gkab1038

Petriman, N. A., Loureiro-Ló pez, M., Taschner, M., Zacharia, N. K.,

Georgieva, M. M., Boegholm, N., Wang, J., Mourao,

̃ A., Russell, R. B.,

Andersen, J. S. et al. (2022). Biochemically validated structural model of the 15subunit intraflagellar transport complex IFT-B. EMBO J. 41, e112440. doi:10.

15252/embj.2022112440

Piersimoni, L., Kastritis, P. L., Arlt, C. and Sinz, A. (2022). Cross-linking mass

spectrometry for investigating protein conformations and protein−protein

interactions: a method for all seasons. Chem. Rev. 122, 7500-7531. doi:10.

1021/acs.chemrev.1c00786

Prevo, B., Scholey, J. M. and Peterman, E. J. G. (2017). Intraflagellar transport:

mechanisms of motor action, cooperation, and cargo delivery. FEBS J. 284,

2905-2931. doi:10.1111/febs.14068

Qiu, H., Tsurumi, Y., Katoh, Y. and Nakayama, K. (2022). Combinations of deletion

and missense variations of the dynein-2 DYNC2LI1 subunit found in skeletal

ciliopathies cause ciliary defects. Sci. Rep. 12, 31. doi:10.1038/s41598-02103950-0

Reiter, J. F. and Leroux, M. R. (2017). Genes and molecular pathways

underpinning ciliopathies. Nat. Rev. Mol. Cell Biol. 18, 533-547. doi:10.1038/

nrm.2017.60

Rosenbaum, J. L. and Witman, G. B. (2002). Intraflagellar transport. Nat. Rev. Mol.

Cell Biol. 3, 813-825. doi:10.1038/nrm952

15

Journal of Cell Science

RESEARCH ARTICLE

Schafer, J. C., Haycraft, C. J., Thomas, J. H., Yoder, B. K. and Swoboda, P.

(2003). XBX-1 encodes a dynein light intermediate chain required for retrograde

intraflagellar transport and cilia assembly in Caenorhabditis elegans. Mol. Biol.

Cell 14, 2057-2070. doi:10.1091/mbc.e02-10-0677

Schmidts, M. (2014). Clinical genetics and pathobiology of ciliary

chondrodysplasias. J. Pediatr. Genet. 3, 49-64. doi:10.3233/PGE-14089

Schmidts, M., Hou, Y., Corté s, C., Mans, D. A., Huber, C., Boldt, K., Patel, M.,

Van Reeuwijk, J., Plaza, J. M., Van Beersum, S. E. C. et al. (2015). TCTEX1D2

mutations underlie Jeune asphyxiating thoracic dystrophy with impaired

retrograde intraflagellar transport. Nat. Commun. 6, 7074. doi:10.1038/

ncomms8074

Takahara, M., Katoh, Y., Nakamura, K., Hirano, T., Sugawa, M., Tsurumi, Y. and

Nakayama, K. (2018). Ciliopathy-associated mutations of IFT122 impair ciliary

protein trafficking but not ciliogenesis. Hum. Mol. Genet. 27, 516-528. doi:10.

1093/hmg/ddx421

Takahashi, S., Kubo, K., Waguri, S., Yabashi, A., Shin, H.-W., Katoh, Y. and

Nakayama, K. (2012). Rab11 regulates exocytosis of recycling vesicles at the

plasma membrane. J. Cell Sci. 125, 4049-4057. doi:10.1242/jcs.102913

Taschner, M. and Lorentzen, E. (2016). The intraflagellar transport machinery.

Cold Spring Harb. Perspect. Biol. 8, a028092. doi:10.1101/cshperspect.a028092

Taschner, M., Weber, K., Mourao,

̃ A., Vetter, M., Awasthi, M., Stiegler, M.,

Bhogaraju, S. and Lorentzen, E. (2016). Intraflagellar transport proteins 172, 80,

57, 54, 38, and 20 form a stable tubulin-binding IFT-B2 complex. EMBO J. 35,

773-790. doi:10.15252/embj.201593164

Thomas, S., Ritter, B., Verbich, D., Sanson, C., Bourbonnière, L.,

Mckinney, R. A. and Mcpherson, P. S. (2009). Intersectin regulates dendritic

spine development and somatodendritic endocytosis but not synaptic vesicle

recycling in hippocampal neurons. J. Biol. Chem. 284, 12410-12419. doi:10.1074/

jbc.M809746200

Toropova, K., Mladenov, K. and Roberts, A. J. (2017). Intraflagellar transport

dynein is autoinhibited by trapping of its mechanical and track-binding elements.

Nat. Struct. Mol. Biol. 24, 461-468. doi:10.1038/nsmb.3391

Toropova, K., Zalyte, R., Mukhopadhyay, A. G., Mladenov, M., Carter, A. P. and

Roberts, A. J. (2019). Structure of the dynein-2 complex and its assembly with

intraflagellar transport trains. Nat. Struct. Mol. Biol. 26, 823-829. doi:10.1038/

s41594-019-0286-y

Tsurumi, Y., Hamada, Y., Katoh, Y. and Nakayama, K. (2019). Interactions of the

dynein-2 intermediate chain WDR34 with the light chains are required for ciliary

retrograde protein trafficking. Mol. Biol. Cell 30, 658-670. doi:10.1091/mbc.E1810-0678

Journal of Cell Science (2023) 136, jcs260462. doi:10.1242/jcs.260462

Tunyasuvunakool, K., Adler, J., Wu, Z., Green, T., Zielinski, M., Žı́dek, A.,

Bridgland, A., Cowie, A., Meyer, C., Laydon, A. et al. (2021). Highly accurate

protein structure prediction for the human proteome. Nature 596, 590-596. doi:10.

1038/s41586-021-03828-1

Van Den Hoek, H., Klena, N., Jordan, M. A., Viar, G. A., Righetto, R. D.,

Schaffer, M., Erdmann, P. S., Wan, W., Geimer, S., Plitzko, J. M. et al. (2022). In

situ architecture of the ciliary base reveals the stepwise assembly of intraflagellar

transport trains. Science 377, 543-548. doi:10.1126/science.abm6704

Vuolo, L., Stevenson, N. L., Heesom, K. J. and Stephens, D. J. (2018). Dynein-2

intermediate chains play crucial but distinct roles in primary cilia formation and

function. Elife 7, e39655. doi:10.7554/eLife.39655

Vuolo, L., Stevenson, N. L., Mukhopadhyay, A. G., Roberts, A. J. and

Stephens, D. J. (2020). Cytoplasmic dynein-2 at a glance. J. Cell Sci. 133,

jcs240614. doi:10.1242/jcs.240614

Webb, S., Mukhopadhyay, A. G. and Roberts, A. J. (2020). Intraflagellar transport

trains and motors: insights from structure. Sem. Cell Dev. Biol. 107, 82-90. doi:10.

1016/j.semcdb.2020.05.021

Wingfield, J. L., Mekonnen, B., Mengoni, I., Liu, P., Jordan, M., Diener, D.,

Pigino, G. and Lechtreck, K. (2021). In vivo imaging shows continued

association of several IFT A, B and dynein complexes while IFT trains U-turn at

the tip. J. Cell Sci. 134, jcs259010. doi:10.1242/jcs.259010

Yang, S., Bahl, K., Chou, H.-T., Woodsmith, J., Stelzl, U., Walz, T. and

Nachury, M. V. (2020). Near-atomic structures of the BBSome reveal the basis for

BBSome activation and binding to GPCR cargoes. Elife 9, e55954. doi:10.7554/

eLife.55954

Ye, F., Nager, A. R. and Nachury, M. V. (2018). BBSome trains remove activated

GPCRs from cilia by enabling passage through the transition zone. J. Cell Biol.

217, 1847-1868. doi:10.1083/jcb.201709041

Zhang, W., Taylor, S. P., Ennis, H. A., Forlenza, K. N., Duran, I., Li, B.,

Ortiz Sanchez, J. A., Nevarez, L., Nickerson, D. A., Bamshad, M. et al. (2018).

Expanding the genetic architecture and phenotypic spectrum in the skeletal

ciliopathy. Hum. Mut. 39, 152-166. doi:10.1002/humu.23362

Zhou, Z., Qiu, H., Castro-Araya, R.-F., Takei, R., Nakayama, K. and Katoh, Y.

(2022). Impaired cooperation between IFT74/BBS22–IFT81 and IFT25–IFT27/

BBS19 in the IFT-B complex causes ciliary defects in Bardet-Biedl syndrome.

Hum. Mol. Genet. 31, 1681-1693. doi:10.1093/hmg/ddab354

Zhu, X., Wang, J., Li, S., Lechtreck, K. and Pan, J. (2021). IFT54 directly interacts

with kinesin-II and IFT dynein to regulate anterograde intraflagellar transport.

EMBO J. 40, e105781. doi:10.15252/embj.2020105781

Journal of Cell Science

RESEARCH ARTICLE

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