Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Citations to this article

A DOCK8-WIP-WASp complex links T cell receptors to the actin cytoskeleton
Erin Janssen, … , Francis W. Luscinskas, Raif S. Geha
Erin Janssen, … , Francis W. Luscinskas, Raif S. Geha
Published September 6, 2016
Citation Information: J Clin Invest. 2016;126(10):3837-3851. https://doi.org/10.1172/JCI85774.
View: Text | PDF
Research Article Immunology Article has an altmetric score of 2

A DOCK8-WIP-WASp complex links T cell receptors to the actin cytoskeleton

  • Text
  • PDF
Abstract

Wiskott-Aldrich syndrome (WAS) is associated with mutations in the WAS protein (WASp), which plays a critical role in the initiation of T cell receptor–driven (TCR-driven) actin polymerization. The clinical phenotype of WAS includes susceptibility to infection, allergy, autoimmunity, and malignancy and overlaps with the symptoms of dedicator of cytokinesis 8 (DOCK8) deficiency, suggesting that the 2 syndromes share common pathogenic mechanisms. Here, we demonstrated that the WASp-interacting protein (WIP) bridges DOCK8 to WASp and actin in T cells. We determined that the guanine nucleotide exchange factor activity of DOCK8 is essential for the integrity of the subcortical actin cytoskeleton as well as for TCR-driven WASp activation, F-actin assembly, immune synapse formation, actin foci formation, mechanotransduction, T cell transendothelial migration, and homing to lymph nodes, all of which also depend on WASp. These results indicate that DOCK8 and WASp are in the same signaling pathway that links TCRs to the actin cytoskeleton in TCR-driven actin assembly. Further, they provide an explanation for similarities in the clinical phenotypes of WAS and DOCK8 deficiency.

Authors

Erin Janssen, Mira Tohme, Mona Hedayat, Marion Leick, Sudha Kumari, Narayanaswamy Ramesh, Michel J. Massaad, Sumana Ullas, Veronica Azcutia, Christopher C. Goodnow, Katrina L. Randall, Qi Qiao, Hao Wu, Waleed Al-Herz, Dianne Cox, John Hartwig, Darrell J. Irvine, Francis W. Luscinskas, Raif S. Geha

×

Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2009 Total
Citations: 2 2 3 7 10 9 13 10 8 1 65
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article (65)

Title and authors Publication Year
Inborn Errors of Immunity Presenting with Early-Onset Severe Atopy
Chuleerarux N, Makkoukdji N, Satnarine T, Kuhn JE, Nopsopon T, Valyasevi P, Schmidt FB, Kleiner G, Gans M
Medicina 2025
Current state of cancer immunity cycle: new strategies and challenges of using precision hydrogels to treat breast cancer
Zhu Y, Su Y, Guo Y, Wang X, Zhang Z, Lu Y, Yang H, Pang H
Frontiers in Immunology 2025
HIV-1 Mediated Cortical Actin Disruption Mirrors ARP2/3 Defects Found in Primary T Cell Immunodeficiencies
Crater JM, Dunn D, Nixon DF, O\u2019Brien RL
2024
B cells require DOCK8 to elicit and integrate T cell help when antigen is limiting
Deobagkar-Lele M, Crawford G, Crockford TL, Back J, Hodgson R, Bhandari A, Bull KR, Cornall RJ
Science immunology 2024
Dendritic cells in inborn errors of immunity
Gupta S, Agrawal A
Frontiers in immunology 2023
DOCK8 is essential for neutrophil mediated clearance of cutaneous S. aureus infection
Wilkie H, Timilshina M, Das M, Pelovitz T, Geha RS
Clinical Immunology 2023
WASP facilitates tumor mechanosensitivity in T lymphocytes
Mandal S, Melo M, Gordiichuk P, Acharya S, Poh YC, Li N, Aung A, Dane EL, Irvine DJ, Kumari S
2023
DOCK8-expressing T follicular helper cells newly generated beyond self-organized criticality cause systemic lupus erythematosus
S Shiozawa, K Tsumiyama, Y Miyazaki, K Uto, K Sakurai, T Nakashima, H Matsuyama, A Doi, M Tarui, M Izumikawa, M Kimura, Y Fujita, C Satonaka, T Horiuchi, T Matsubara, M Oribe, T Yamane, H Kagawa, QZ Li, K Mizuno, Y Mukai, K Murakami, T Enya, S Tsukimoto, Y Hakata, M Miyazawa, K Shiozawa
iScience 2022
CRISPR/Cas-Based Gene Editing Strategies for DOCK8 Immunodeficiency Syndrome
S Ravendran, S Hernández, S König, R Bak
2022
Inborn Errors of the Immune System Associated With Atopy
Nelson RW, Geha RS, McDonald DR
Frontiers in immunology 2022
The Pathophysiological Roles of Regulatory T Cells in the Early Phase of Systemic Sclerosis
Kobayashi S, Nagafuchi Y, Shoda H, Fujio K
Frontiers in immunology 2022
Allergic manifestations of inborn errors of immunity and their impact on the diagnosis: A worldwide study.
El-Sayed ZA, El-Ghoneimy DH, Ortega-Martell JA, Radwan N, Aldave JC, Al-Herz W, Al-Nesf MA, Condino-Neto A, Cole T, Eley B, Erwa NHH, Espinosa-Padilla S, Faria E, Rosario Filho NA, Fuleihan R, Galal N, Garabedian E, Hintermeyer M, Imai K, Irani C, Kamal E, Kechout N, Klocperk A, Levin M, Milota T, Ouederni M, Paganelli R, Pignata C, Qamar FN, Quinti I, Qureshi S, Radhakrishnan N, Rezaei N, Routes J, Singh S, Siniah S, Abdel-Hakam Taha I, Tanno LK, Van Dort B, Volokha A, Sullivan K
The World Allergy Organization journal 2022
dock8 deficiency attenuates microglia colonization in early zebrafish larvae.
Wu L, Xue R, Chen J, Xu J
Cell Death Discovery 2022
Deciphering the role of DOCK8 in tumorigenesis by regulating immunity and the application of nanotechnology in DOCK8 deficiency therapy
Zhang L, Cao Y, Dai X, Zhang X
Frontiers in pharmacology 2022
Somatic reversion of pathogenic DOCK8 variants alters lymphocyte differentiation and function to effectively cure DOCK8 deficiency
Bethany A. Pillay, Mathieu Fusaro, Paul E. Gray, Aaron Luke Statham, Leslie Burnett, Liliana Bezrodnik, Alisa Kane, Winnie W. Y. Tong, Chrystelle Abdo, Sarah Winter, Samuel Chevalier, Romain Levy, Cécile Masson, Yohann Schmitt, Christine Bole-Feysot, Marion Malphettes, Elizabeth Macintyre, Jean-Pierre de Villartay, John B. Ziegler, Joanne M. Smart, Jane Peake, Asghar Aghamohammadi, Lennart Hammarström, Hassan Abolhassani, Capucine Picard, Alain Fischer, Sylvain Latour, Benedicte Neven, Stuart Tangye, Cindy S. Ma
Journal of Clinical Investigation 2021
ARPC1B binds WASP to control actin polymerization and curtail tonic signaling in B cells
Gabriella Leung, Yuhuan Zhou, Philip Ostrowski, Sivakami Mylvaganam, Parastoo Boroumand, Daniel J Mulder, Conghui Guo, Aleixo M Muise, Spencer Freeman
JCI Insight 2021
DOCK8 Expression in Regulatory T Cells Maintains their Stability and Limits Contact Hypersensitivity
H Wilkie, E Janssen, JM Leyva-Castillo, RS Geha
Journal of Investigative Dermatology 2021
Actin Dynamics at the T Cell Synapse as Revealed by Immune-Related Actinopathies
L Dupré, K Boztug, L Pfajfer
Frontiers in Cell and Developmental Biology 2021
Molecular Tuning of Actin Dynamics in Leukocyte Migration as Revealed by Immune-Related Actinopathies
A Kamnev, C Lacouture, M Fusaro, L Dupré
Frontiers in immunology 2021
Inborn errors of immunity with atopic phenotypes: A practical guide for allergists
R Castagnoli, V Lougaris, G Giardino, S Volpi, L Leonardi, FL Torre, S Federici, S Corrente, BL Cinicola, A Soresina, C Cancrini, GL Marseglia, F Cardinale
World Allergy Organization Journal 2021
The RHO Family GTPases: Mechanisms of Regulation and Signaling
N Mosaddeghzadeh, MR Ahmadian
Cells 2021
DOCK8 deficiency diminishes thymic T‐regulatory cell development but not thymic deletion
KL Randall, HD Law, AF Ziolkowski, RC Wirasinha, CC Goodnow, SR Daley
IBMS BoneKEy 2021
A conserved PI(4,5)P2–binding domain is critical for immune regulatory function of DOCK8
T Sakurai, M Kukimoto-Niino, K Kunimura, N Yamane, D Sakata, R Aihara, T Yasuda, S Yokoyama, M Shirouzu, Y Fukui, T Uruno
2021
Variable Distribution of DOCK-D Proteins between Cytosol and Nucleoplasm in Cell Lines, Effect of Interleukin-4 on DOCK10 in B-Cell Lymphoid Neoplasms, and Validation of a New DOCK10 Antiserum for Immunofluorescence Studies
N Ruiz-Lafuente, A Minguela, JM Moraleda, M Muro, A Parrado
Antibodies 2021
DOCK8 is essential for LFA-1 dependent positioning of T follicular helper cells in germinal centers
Erin Janssen, Mira Tohme, Jordan Butts, Sophie S.B. Giguere, Peter T. Sage, Francisco E. Velázquez, Christy Kam, Elena Milin, Mrinmoy Das, Ali Sobh, Salem Al-Tamemi, Francis W. Luscinskas, Facundo Batista, Raif S. Geha
JCI Insight 2020
WASP and Mst1 coregulate B-cell development and B-cell receptor signaling
L Huang, X Sun, D Yang, X Dai, P Jiang, X Bai, Y Zhang, J Wang, W Li, H Miller, W Song, B Treanor, X Zhao, C Liu
Blood Advances 2020
The cytoskeletal regulator HEM1 governs B cell development and prevents autoimmunity
E Salzer, S Zoghi, MG Kiss, F Kage, C Rashkova, S Stahnke, M Haimel, R Platzer, M Caldera, RC Ardy, B Hoeger, J Block, D Medgyesi, C Sin, S Shahkarami, R Kain, V Ziaee, P Hammerl, C Bock, J Menche, L Dupré, JB Huppa, M Sixt, A Lomakin, K Rottner, CJ Binder, TE Stradal, N Rezaei, K Boztug
Science Immunology 2020
Expression of a TMC6-TMC8-CIB1 heterotrimeric complex in lymphocytes is regulated by each of the components
CJ Wu, X Li, CL Sommers, K Kurima, S Huh, G Bugos, L Dong, W Li, AJ Griffith, LE Samelson
The Journal of biological chemistry 2020
Impact of extracellular matrix stiffness on genomic heterogeneity in MYCN-amplified neuroblastoma cell line
A López-Carrasco, S Martín-Vañó, R Burgos-Panadero, E Monferrer, AP Berbegall, B Fernández-Blanco, S Navarro, R Noguera
Journal of Experimental & Clinical Cancer Research 2020
Migration-induced cell shattering due to DOCK8 deficiency causes a type 2–biased helper T cell response
C Schneider, C Shen, AA Gopal, T Douglas, B Forestell, KD Kauffman, D Rogers, P Artusa, Q Zhang, H Jing, AF Freeman, DL Barber, IL King, M Saleh, PW Wiseman, HC Su, JN Mandl
Nature Immunology 2020
NCKAP1L defects lead to a novel syndrome combining immunodeficiency, lymphoproliferation, and hyperinflammation
CN Castro, M Rosenzwajg, R Carapito, M Shahrooei, M Konantz, A Khan, Z Miao, M Groß, T Tranchant, M Radosavljevic, N Paul, T Stemmelen, F Pitoiset, A Hirschler, B Nespola, A Molitor, V Rolli, A Pichot, LE Faletti, B Rinaldi, S Friant, M Mednikov, H Karauzum, MJ Aman, C Carapito, C Lengerke, V Ziaee, W Eyaid, S Ehl, F Alroqi, N Parvaneh, S Bahram
Journal of Experimental Medicine 2020
The DISC1-Girdin complex: a missing link in signaling to the T cell cytoskeleton
N Maskalenko, S Nath, A Ramakrishnan, N Anikeeva, Y Sykulev, M Poenie
Journal of cell science 2020
RasGRP1 is a causal factor in the development of l -DOPA–induced dyskinesia in Parkinson’s disease
M Eshraghi, UN Ramírez-Jarquín, N Shahani, T Nuzzo, AD Rosa, S Swarnkar, N Galli, O Rivera, G Tsaprailis, C Scharager-Tapia, G Crynen, Q Li, ML Thiolat, E Bezard, A Usiello, S Subramaniam
Science Advances 2020
Hematopoietic Stem Cell Transplantation in Primary Immunodeficiency Diseases: Current Status and Future Perspectives
R Castagnoli, OM Delmonte, E Calzoni, LD Notarangelo
Frontiers in Pediatrics 2019
Host–microbial dialogues in atopic dermatitis
T Kobayashi, K Nagao
International Immunology 2019
DOCK8 is expressed in microglia, and it regulates microglial activity during neurodegeneration in murine disease models
K Namekata, X Guo, A Kimura, N Arai, C Harada, T Harada
The Journal of biological chemistry 2019
The Coordination Between B Cell Receptor Signaling and the Actin Cytoskeleton During B Cell Activation
J Li, W Yin, Y Jing, D Kang, L Yang, J Cheng, Z Yu, Z Peng, X Li, Y Wen, X Sun, B Ren, C Liu
Frontiers in immunology 2019
Congenital Defects in Actin Dynamics of Germinal Center B Cells
M He, LS Westerberg
Frontiers in immunology 2019
Human DOCK2 Deficiency: Report of a Novel Mutation and Evidence for Neutrophil Dysfunction
L Moens, M Gouwy, B Bosch, O Pastukhov, A Nieto-Patlàn, U Siler, G Bucciol, D Mekahli, F Vermeulen, L Desmet, S Maebe, H Flipts, A Corveleyn, D Moshous, P Philippet, SG Tangye, B Boisson, JL Casanova, B Florkin, S Struyf, J Reichenbach, J Bustamante, LD Notarangelo, I Meyts
Journal of Clinical Immunology 2019
Origin, Organization, Dynamics, and Function of Actin and Actomyosin Networks at the T Cell Immunological Synapse
JA Hammer, JC Wang, M Saeed, AT Pedrosa
Annual Review of Immunology 2019
A composition-dependent molecular clutch between T cell signaling condensates and actin
JA Ditlev, AR Vega, DV Köster, X Su, T Tani, AM Lakoduk, RD Vale, S Mayor, K Jaqaman, MK Rosen
eLife 2019
T Cell Microvilli: Sensors or Senders?
HR Kim, CD Jun
Frontiers in immunology 2019
NKG2D–DAP10 signaling recruits EVL to the cytotoxic synapse to generate F-actin and promote NK cell cytotoxicity
KM Wilton, BL Overlee, DD Billadeau
Journal of cell science 2019
Cytoskeletal tension actively sustains the migratory T‐cell synaptic contact
S Kumari, M Mak, YC Poh, M Tohme, N Watson, M Melo, E Janssen, M Dustin, R Geha, DJ Irvine
The EMBO Journal 2019
DOCK family proteins: key players in immune surveillance mechanisms
K Kunimura, T Uruno, Y Fukui
International Immunology 2019
B cells extract antigens at Arp2/3-generated actin foci interspersed with linear filaments
SI Roper, L Wasim, D Malinova, M Way, S Cox, P Tolar
eLife 2019
WASP-mediated regulation of anti-inflammatory macrophages is IL-10 dependent and is critical for intestinal homeostasis
A Biswas, DS Shouval, A Griffith, JA Goettel, M Field, YH Kang, L Konnikova, E Janssen, NS Redhu, AJ Thrasher, T Chatila, VK Kuchroo, RS Geha, LD Notarangelo, SY Pai, BH Horwitz, SB Snapper
Nature Communications 2018
Primary atopic disorders
JJ Lyons, JD Milner
Journal of Experimental Medicine 2018
Human hyper-IgE syndrome: singular or plural?
Q Zhang, B Boisson, V Béziat, A Puel, JL Casanova
Mammalian Genome 2018
TCR Signaling Abnormalities in Human Th2-Associated Atopic Disease
JD Milner
Frontiers in immunology 2018
Hippo Kinases Mst1 and Mst2 Sense and Amplify IL-2R−STAT5 Signaling in Regulatory T Cells to Establish Stable Regulatory Activity
H Shi, C Liu, H Tan, Y Li, TL Nguyen, Y Dhungana, C Guy, P Vogel, G Neale, S Rankin, Y Feng, J Peng, W Tao, H Chi
Immunity 2018
Interaction of septin 7 and DOCK8 in equine lymphocytes reveals novel insights into signaling pathways associated with autoimmunity
M Schauer, KJ Kleinwort, RL Degroote, C Wiedemann, E Kremmer, SM Hauck, CA Deeg
Scientific Reports 2018
Dock8 regulates BCR signaling and activation of memory B cells via WASP and CD19
X Sun, J Wang, T Qin, Y Zhang, L Huang, L Niu, X Bai, Y Jing, X Xuan, H Miller, Y Zhao, W Song, X Tang, Z Zhang, X Zhao, C Liu
Blood Advances 2018
The Lack of WIP Binding to Actin Results in Impaired B Cell Migration and Altered Humoral Immune Responses
SJ Keppler, M Burbage, F Gasparrini, L Hartjes, S Aggarwal, MJ Massaad, RS Geha, A Bruckbauer, FD Batista
Cell Reports 2018
Crosstalk between WIP and Rho family GTPases
IM Antón, C Gómez-Oro, S Rivas, F Wandosell
Small GTPases 2018
Insights into immunity from clinical and basic science studies of DOCK8 immunodeficiency syndrome
HC Su, H Jing, P Angelus, AF Freeman
Immunological Reviews 2018
DOCK8 enforces immunological tolerance by promoting IL-2 signaling and immune synapse formation in Treg cells
Erin Janssen, Sudha Kumari, Mira Tohme, Sumana Ullas, Victor Barrera, Jeroen Tas, Marcela Castillo-Rama, Roderick T. Bronson, Shariq Usmani, Darrell Irvine, Thorsten Mempel, Raif Geha
JCI Insight 2017
Wiskott-Aldrich syndrome protein: Emerging mechanisms in immunity
E Rivers, AJ Thrasher
European Journal of Immunology 2017
DOCK8 Deficiency Presenting as an IPEX-Like Disorder
FJ Alroqi, LM Charbonnier, S Keles, F Ghandour, P Mouawad, R Sabouneh, R Mohammed, A Almutairi, J Chou, MJ Massaad, RS Geha, Z Baz, TA Chatila
Journal of Clinical Immunology 2017
DOCK8 regulates signal transduction events to control immunity
CJ Kearney, KL Randall, J Oliaro
Cellular and Molecular Immunology 2017
Negative Regulation of Type 2 Immunity
DA de Kouchkovsky, S Ghosh, CV Rothlin
Trends in Immunology 2017
DOCK8 deficiency: Insights into pathophysiology, clinical features and management
CM Biggs, S Keles, TA Chatila
Clinical Immunology 2017
Cytoskeletal control of B cell responses to antigens
P Tolar
Nature Reviews Immunology 2017
Migratory CD11b + conventional dendritic cells induce T follicular helper cell–dependent antibody responses
JK Krishnaswamy, U Gowthaman, B Zhang, J Mattsson, L Szeponik, D Liu, R Wu, T White, S Calabro, L Xu, MA Collet, M Yurieva, S Alsén, P Fogelstrand, A Walter, WR Heath, SN Mueller, U Yrlid, A Williams, SC Eisenbarth
Science Immunology 2017
Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2009

← Previous 1 2 3 Next →

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Posted by 3 X users
95 readers on Mendeley
See more details