H-Ras induces exuberant de novo dendritic protrusion growth in mature neurons regardless of cell type
Sarah Krüssel,
Ishana Deb,
Seungkyu Son,
Gabrielle Ewall,
Minhyeok Chang,
Hey-Kyoung Lee,
Won Do Heo,
Hyung-Bae Kwon
Affiliations
Sarah Krüssel
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Ishana Deb
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Seungkyu Son
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
Gabrielle Ewall
Solomon H. Snyder Department of Neuroscience, Zanvyl-Krieger Mind/Brain Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA
Minhyeok Chang
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Hey-Kyoung Lee
Solomon H. Snyder Department of Neuroscience, Zanvyl-Krieger Mind/Brain Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA; Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD, USA
Won Do Heo
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
Hyung-Bae Kwon
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Corresponding author
Summary: Dendritic protrusions, mainly spines and filopodia, correlate with excitatory synapses in pyramidal neurons (PyNs), but this relationship may not apply universally. We found that ectopic H-Ras expression increased protrusions across various cortical cell types, including layer 2/3 PyNs, parvalbumin (PV)-, and vasoactive intestinal peptide (VIP)-positive interneurons (INs) in the primary motor cortex. The probability of detecting protrusions correlated with local H-Ras activity, indicating its role in protrusion formation. H-Ras overexpression led to high turnover rates by adding protrusions. Two-photon photolysis of glutamate induced de novo spine formation in mature H-Ras expressing neurons, suggesting H-Ras’s effect is not limited to early development. In PyNs and PV-INs, but not VIP-INs, spine neck lengths shifted to filopodia-like phenotypes. H-Ras primarily induced filopodia in PyNs and spines in PV- and VIP-INs. Increased protrusions in H-Ras-transfected PyNs lacked key excitatory synaptic proteins and did not affect miniature excitatory postsynaptic currents (mEPSCs), suggesting multifaceted roles beyond excitatory synapses.
