NYAP: a phosphoprotein family that links PI3K to WAVE1 signalling in neurons
Open accessAbstract
The phosphoinositide 3-kinase (PI3K) pathway has been extensively studied in neuronal function and morphogenesis. However, the precise molecular mechanisms of PI3K activation and its downstream signalling in neurons remain elusive. Here, we report the identification of the Neuronal tYrosine-phosphorylated Adaptor for the PI 3-kinase (NYAP) family of phosphoproteins, which is composed of NYAP1, NYAP2, and Myosin16/NYAP3. The NYAPs are expressed predominantly in developing neurons. Upon stimulation with Contactin5, the NYAPs are tyrosine phosphorylated by Fyn. Phosphorylated NYAPs interact with PI3K p85 and activate PI3K, Akt, and Rac1. Moreover, the NYAPs interact with the WAVE1 complex which mediates remodelling of the actin cytoskeleton after activation by PI3K-produced PIP(3) and Rac1. By simultaneously interacting with PI3K and the WAVE1 complex, the NYAPs bridge a PI3K-WAVE1 association. Disruption of the NYAP genes in mice affects brain size and neurite elongation. In conclusion, the NYAPs activate PI3K and concomitantly recruit the downstream effector WAVE complex to the close vicinity of PI3K and regulate neuronal morphogenesis.
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The WAVE1 complex interacts with NYAP family proteins and is involved in PI3K-mediated neurite outgrowth and neuronal morphogenesis.
“The WAVE1 complex interacts with NYAP (Neuronal tYrosine‐phosphorylated Adaptor for the PI 3‐kinase) family proteins and is involved in PI3K-mediated neurite outgrowth and neuronal morphogenesis72.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [72]
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- Authors
- Yokoyama, K., Tezuka, T., Kotani, M., Nakazawa, T., Hoshina, N., Shimoda, Y., Kakuta, S., Sudo, K., Watanabe, K., Iwakura, Y., & Yamamoto, T.
- Affiliations
- Institute of Medical Science, The University of Tokyo (JP)
- Ohu University (JP)
- Okinawa Institute of Science and Technology Graduate University (JP)
- Nagaoka University of Technology (JP)
- Japan Science and Technology Agency (JP)
- Corresponding author
- Yamamoto, Tadashi
- ORCID
- Venue
- The EMBO Journal
- Published
- 2011-09-23
- Volume
- 30
- Issue
- 23
- Pages
- 4739-4754
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC3243607
- OpenAlex
- W2102045372
- Cited by
- 75
- References
- 6
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 4 · 2023: 5 · 2022: 3 · 2021: 6 · 2020: 6 · 2019: 15 · 2017: 4 · 2016: 5 · 2015: 7 · 2014: 1 · 2013: 3
- FWCI
- 0.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science (21680033, 22700391, 21229006, 20220009, 22700448)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Keywords
- phosphatidylinositol 3-kinase, neuronal morphogenesis, neurite outgrowth, actin cytoskeleton remodeling, Fyn tyrosine kinase, tyrosine phosphorylation, PI3K p85, Akt, Rac1, phosphatidylinositol 3,4,5-trisphosphate, brain size, developing neurons
- MeSH terms
- Actins, Animals, Brain, Cytoskeleton, HeLa Cells, Humans, Mice, Inbred C57BL, Models, Biological, Phosphorylation, Tyrosine, Signal Transduction, Neurites, Sequence Homology, Amino Acid, Mice, Knockout, Neocortex, Phosphatidylinositol 3-Kinases, Adaptor Proteins, Signal Transducing, Proto-Oncogene Proteins c-fyn, Wiskott-Aldrich Syndrome Protein Family, Mice
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