Ndr2 Kinase Controls Neurite Outgrowth and Dendritic Branching Through α1 Integrin Expression
Open accessAbstract
The serine / threonine kinase Ndr2 has been shown to control the inside-out activation of the β1 subunit of integrins and the formation of neurites in both primary neurons and neurally differentiated pheochromacytoma (PC12) cells. In this study, we demonstrate that Ndr2 kinase furthermore determines the substrate specificity of neurite extension in PC12 cells via expression of α1β1 integrins. We show that stable overexpression of Ndr2 in PC12 cells increases neurite growth and extension on poly-D-lysine substrate, likely involving an increased expression of active β1 integrin in the growth tips of these cells. By contrast, the Ndr2 overexpressing cells do not show the α1β1 integrin-mediated enhancement of neurite growth on collagen IV substrate that can be seen in control cells. Moreover, they entirely fail to increase in response to activation of α1β1 integrins via a soluble KTS ligand and show a diminished accumulation of α1 integrin in neurite tips, although the expression of this subunit is induced during differentiation to comparable levels as in control cells. Finally, we demonstrate that Ndr2 overexpression similarly inhibits the α1β1 integrin-dependent dendritic growth of primary hippocampal neurons on laminin 111 substrate. By contrast, lack of Ndr2 impairs the dendritic growth regardless of the substrate. Together, these results suggest that Ndr2 regulates α1 integrin trafficking in addition to β1 integrin subunit activation and thereby controls the neurite growth on different extracellular matrix substrates.
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NDR2 is the principal NDR kinase in the mouse CNS.
“NDR2 is the principal NDR kinase in the mouse CNS, where it has been shown to regulate integrin‐dependent dendritic branching as well as growth and plasticity in hippocampal mossy fibers.”
From The Serine/Threonine Kinase <scp>NDR2</scp> Regulates Integrin Signaling, Synapse Formation, and Synaptic Plasticity in the Hippocampus (2025) · cites this paper as Demiray et al. 2018
The Introduction (page unavailable) describes prominent Ndr2 expression in the central nervous system. It does not establish that Ndr2 is the principal NDR kinase in the mouse CNS relative to other family members. (LLM, conf=0.82)
Experimental — accuracy not yet measuredNDR2 controls dendritic branching during the postnatal development of pyramidal neurons in hippocampal area CA3.
“We showed that it controls the dendritic branching during the postnatal development of pyramidal neurons in hippocampal area CA3, growth, and plasticity of hippocampal mossy fibres (Demiray et al. 2018;”
From The Serine/Threonine Kinase <scp>NDR2</scp> Regulates Integrin Signaling, Synapse Formation, and Synaptic Plasticity in the Hippocampus (2025) · cites this paper as Demiray et al. 2018
The Results section, “Ndr2 Controls Dendritic Branching in Primary Neurons” (page unavailable), shows that changing Ndr2 expression affects dendritic branching in cultured hippocampal neurons. The Methods section, “Primary Cell Culture” (page unavailable), identifies those neurons as derived from embryonic mouse hippocampi; the cited study does not establish the claim specifically for postnatal CA3 pyramidal neurons. (LLM, conf=0.88)
Experimental — accuracy not yet measuredNDR2 is the only NDR kinase expressed in the adult mouse brain.
“Previously, we showed that from the mammalian NDR kinases, NDR2 is the only one expressed in the adult mouse brain.”
From The Serine/Threonine Kinase <scp>NDR2</scp> Regulates Integrin Signaling, Synapse Formation, and Synaptic Plasticity in the Hippocampus (2025) · cites this paper as Demiray et al. 2018
The Introduction (page unavailable) reports prominent Ndr2 expression in the central nervous system. It does not establish that Ndr2 is the only NDR kinase expressed in the adult mouse brain; the passages found do not compare adult-mouse-brain expression across the kinase family. (LLM, conf=0.84)
Experimental — accuracy not yet measuredNDR2 controls growth and plasticity of hippocampal mossy fibres.
“We showed that it controls the dendritic branching during the postnatal development of pyramidal neurons in hippocampal area CA3, growth, and plasticity of hippocampal mossy fibres (Demiray et al. 2018;”
From The Serine/Threonine Kinase <scp>NDR2</scp> Regulates Integrin Signaling, Synapse Formation, and Synaptic Plasticity in the Hippocampus (2025) · cites this paper as Demiray et al. 2018
The Results section, “Ndr2 Controls Dendritic Branching in Primary Neurons” (page unavailable), shows that Ndr2 affects dendritic growth in cultured hippocampal neurons. The Introduction also reports earlier findings on hippocampal axonal growth. Neither passage establishes that Ndr2 controls the growth or plasticity of hippocampal mossy fibres specifically. (LLM, conf=0.83)
Experimental — accuracy not yet measuredIn developing neurons, the dendritic growth effects of NDR2 are at least in part mediated by control of intracellular trafficking and recycling of β1 integrins.
“In developing neurons, the dendritic growth effects of NDR2 are at least in part mediated by a control in the intracellular trafficking and recycling of β1 integrins (Rehberg et al. 2014; Demiray et al. 2018).”
From The Serine/Threonine Kinase <scp>NDR2</scp> Regulates Integrin Signaling, Synapse Formation, and Synaptic Plasticity in the Hippocampus (2025) · cites this paper as Demiray et al. 2018
NDR2 expression is low after birth and steadily increases during postnatal development in the mouse brain.
“NDR2 expression is low after birth and steadily increases during postnatal development, whereas NDR1 expression remains completely absent.”
From The Serine/Threonine Kinase <scp>NDR2</scp> Regulates Integrin Signaling, Synapse Formation, and Synaptic Plasticity in the Hippocampus (2025) · cites this paper as Demiray et al. 2018
The Introduction describes prominent Ndr2 expression in the central nervous system, but gives no expression levels at birth or postnatal time course. Searches for postnatal expression and developmental changes found no passage establishing a steady increase in the mouse brain. (LLM, conf=0.72)
Experimental — accuracy not yet measuredNDR1 expression remains completely absent in the mouse brain.
“NDR2 expression is low after birth and steadily increases during postnatal development, whereas NDR1 expression remains completely absent.”
From The Serine/Threonine Kinase <scp>NDR2</scp> Regulates Integrin Signaling, Synapse Formation, and Synaptic Plasticity in the Hippocampus (2025) · cites this paper as Demiray et al. 2018
The Introduction (page not provided) identifies Ndr1 as a close homolog of Ndr2 but does not say whether Ndr1 is expressed in the mouse brain. Searches for Ndr1 expression and postnatal development found no passage establishing that its expression remains absent. (LLM, conf=0.74)
Experimental — accuracy not yet measured
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Cites
Neuronal Functions of the Novel Serine/Threonine Kinase Ndr2
Stork, O., Zhdanov, A., Kudersky, A., Yoshikawa, T., Obata, K., & Pape, H.-C. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403552200 · Cited by 55 · see citing works
Self-citationYang, R., Kong, E., Jin, J., Hergovich, A., & Püschel, A. W. (2014) · Journal of Cell Science · doi:10.1242/jcs.146696 · Cited by 25 · cited 1× · see citing works
“Further research confirmed that Ndr2 is indeed critical for neuronal polarization (Yang et al., 2014) and dendritic differentiation in mammalian neurons.”
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Madencioglu, D. A., Çalışkan, G., Yuanxiang, P., Rehberg, K., Demiray, Y. E., Kul, E., Engler, A., Hayani, H., Bergado-Acosta, J. R., Kummer, A., et al. (2021) · iScience · doi:10.1016/j.isci.2021.102868 · Cited by 8 · see citing works
Self-citationdel Ángel, M., Tsutiya, A., Hayani, H., Madencioglu, D., Kul, E., Caliskan, G., Demiray, Y. E., Dityatev, A., & Stork, O. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70094 · Cited by 1 · see citing works
Self-citation
- Authors
- Demiray, Y. E., Rehberg, K., Kliche, S., & Stork, O.
- Affiliations
- Otto-von-Guericke-Universität Magdeburg (DE)
- Center for Behavioral Brain Sciences (DE)
- Corresponding author
- Stork, Oliver
- Venue
- Frontiers in Molecular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2018-03-06
- Volume
- 11
- Pages
- 66-66
- ISSN
- 1662-5099 (ISSN-L)
- PMC
- PMC5845635
- OpenAlex
- W2794391408
- Cited by
- 12
- References
- 2
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 1
- FWCI
- 0.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Molecular Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Deutsche Forschungsgemeinschaft (GRK1167/P13, STO488/4, CRC854/B10)
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- neurite outgrowth, dendritic branching, integrin alpha1, beta1 integrin, PC12 cells, hippocampal neurons, laminin-111, type IV collagen, extracellular matrix substrates, integrin trafficking, neuronal differentiation
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