Endophilin A1 Promotes Actin Polymerization in Dendritic Spines Required for Synaptic Potentiation

Yang, Yanrui; Chen, Jiang; Guo, Zhenzhen; Deng, Shikun; Du, Xiangyang; Zhu, Shunyi; Ye, Chang; Shi, Yun; Li, Jiajia

doi:10.3389/fnmol.2018.00177

Cited by 20 publications

(34 citation statements)

References 55 publications

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“…Primary mouse cortical neuron isolation and culture in a microfluidic device. Primary mouse forebrain cortical neurons were prepared from embryonic day 16.5 (E16.5) C57BL/6 mouse embryos according to a protocol described previously (56,57). Briefly, forebrain tissues were dissected from E16.5 C57BL/6 mouse embryos, dissociated with 0.125% trypsin in Hanks' balanced salt solution without Ca 2ϩ and Mg 2ϩ at 37°C for 15 min, and triturated in serum-free neurobasal (NB) medium supplemented with 2% B27 supplement and GlutaMAX (Life Technologies, USA).…”

Section: Methodsmentioning

confidence: 99%

Anterograde Viral Tracer Herpes Simplex Virus 1 Strain H129 Transports Primarily as Capsids in Cortical Neuron Axons

Xiao

Zhou

Qin

et al. 2020

J Virol

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The features of herpes simplex virus 1 (HSV-1) strain 129 (H129), including natural neurotropism and anterograde transneuronal trafficking, make it a potential tool for anterograde neural circuitry tracing. Recently anterograde polysynaptic and monosynaptic tracers were developed from H129 and have been applied for the identification of novel connections and functions of different neural circuitries. However, how H129 viral particles are transported in neurons, especially those of the central nervous system, remains unclear. In this study, we constructed recombinant H129 variants with mCherry-labeled capsids and/or green fluorescent protein (GFP)-labeled envelopes and infected the cortical neurons to study axonal transport of H129 viral particles. We found that different types of viral particles were unevenly distributed in the nucleus, cytoplasm of the cell body, and axon. Most H129 progeny particles were unenveloped capsids and were transported as capsids rather than virions in the axon. Notably, capsids acquired envelopes at axonal varicosities and terminals where the sites forming synapses are connected with other neurons. Moreover, viral capsids moved more frequently in the anterograde direction in axons, with an average velocity of 0.62 ± 0.18 μm/s and maximal velocity of 1.80 ± 0.15 μm/s. We also provided evidence that axonal transport of capsids requires the kinesin-1 molecular motor. These findings support that H129-derived tracers map the neural circuit anterogradely and possibly transsynaptically. These data will guide future modifications and improvements of H129-based anterograde viral tracers. IMPORTANCE Anterograde transneuronal tracers derived from herpes simplex virus 1 (HSV-1) strain 129 (H129) are important tools for mapping neural circuit anatomic and functional connections. It is, therefore, critical to elucidate the transport pattern of H129 within neurons and between neurons. We constructed recombinant H129 variants with genetically encoded fluorescence-labeled capsid protein and/or glycoprotein to visualize viral particle movement in neurons. Both electron microscopy and light microscopy data show that H129 capsids and envelopes move separately, and notably, capsids are enveloped at axonal varicosity and terminals, which are the sites forming synapses to connect with other neurons. Superresolution microscopy-based colocalization analysis and inhibition of H129 particle movement by inhibitors of molecular motors support that kinesin-1 contributes to the anterograde transport of capsids. These results shed light into the mechanisms for anterograde transport of H129-derived tracer in axons and transmission between neurons via synapses, explaining the anterograde labeling of neural circuits by H129-derived tracers.

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Section: Methodsmentioning

confidence: 99%

Anterograde Viral Tracer Herpes Simplex Virus 1 Strain H129 Transports Primarily as Capsids in Cortical Neuron Axons

Xiao

Zhou

Qin

et al. 2020

J Virol

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“…Participate along with dynamin and the actin cytoskeleton in plasma membrane invagination during endocytosis (Itoh et al 2005) In cells lacking dynamin, actin-nucleating proteins, actin, and several BAR domain proteins (Endophilin, BINs, SNX9, and SNX18) accumulate at the base of arrested endocytic clathrin-coated pits, where they support the growth of dynamic long tubular necks (Ferguson et al 2009) Directly interact with both lamellipodin and MENA to mediate EGFR endocytosis in an actin-dependent manner (Vehlow et al 2013) Act together with dynamin and actin to drive a fast form of clathrin-independent endocytosis at PIP2-rich sites (Boucrot et al 2015; Renard et al 2015) Promotes actin polymerization in dendritic spines and its loss causes impaired AMPA receptor-mediated synaptic transmission and long-term potentiation (Yang et al 2018) RICHs RICH1 (ARHGAP17) regulates Rho GTPases through its GAP domain to mediate the formation of stress fibers and focal adhesions in platelets (Beck et al 2013) RICH2's (ARHGAP44) recruitment to nanoscale membrane deformations limits filopodia initiation via Rac inhibition mediated by its GAP domain, which in turn reduces actin polymerization required for filopodia formation (Galic et al 2014) GRAFs…”

Section: Rich1mentioning

confidence: 99%

BAR domain proteins—a linkage between cellular membranes, signaling pathways, and the actin cytoskeleton

2018

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Actin filament assembly typically occurs in association with cellular membranes. A large number of proteins sit at the interface between actin networks and membranes, playing diverse roles such as initiation of actin polymerization, modulation of membrane curvature, and signaling. Bin/Amphiphysin/Rvs (BAR) domain proteins have been implicated in all of these functions. The BAR domain family of proteins comprises a diverse group of multi-functional effectors, characterized by their modular architecture. In addition to the membrane-curvature sensing/inducing BAR domain module, which also mediates antiparallel dimerization, most contain auxiliary domains implicated in protein-protein and/or protein-membrane interactions, including SH3, PX, PH, RhoGEF, and RhoGAP domains. The shape of the BAR domain itself varies, resulting in three major subfamilies: the classical crescent-shaped BAR, the more extended and less curved F-BAR, and the inverse curvature I-BAR subfamilies. Most members of this family have been implicated in cellular functions that require dynamic remodeling of the actin cytoskeleton, such as endocytosis, organelle trafficking, cell motility, and T-tubule biogenesis in muscle cells. Here, we review the structure and function of mammalian BAR domain proteins and the many ways in which they are interconnected with the actin cytoskeleton.

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“…However, deletion of endophilin A1 and A2 or all endophilin A families results in neurodegeneration and perinatal lethality, respectively [ 22 , 30 ]. Endophilin A1 is highly expressed in the hippocampal CA1 and CA3 regions, and deletion of endophilin A1 and A2 shows significant decrease in spine size in these hippocampal regions [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Tat-Endophilin A1 Fusion Protein Protects Neurons from Ischemic Damage in the Gerbil Hippocampus: A Possible Mechanism of Lipid Peroxidation and Neuroinflammation Mitigation as Well as Synaptic Plasticity

Jung

Kwon

Kim

et al. 2021

Cells

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The present study explored the effects of endophilin A1 (SH3GL2) against oxidative damage brought about by H2O2 in HT22 cells and ischemic damage induced upon transient forebrain ischemia in gerbils. Tat-SH3GL2 and its control protein (Control-SH3GL2) were synthesized to deliver it to the cells by penetrating the cell membrane and blood–brain barrier. Tat-SH3GL2, but not Control-SH3GL2, could be delivered into HT22 cells in a concentration- and time-dependent manner and the hippocampus 8 h after treatment in gerbils. Tat-SH3GL2 was stably present in HT22 cells and degraded with time, by 36 h post treatment. Pre-incubation with Tat-SH3GL2, but not Control-SH3GL2, significantly ameliorated H2O2-induced cell death, DNA fragmentation, and reactive oxygen species formation. SH3GL2 immunoreactivity was decreased in the gerbil hippocampal CA1 region with time after ischemia, but it was maintained in the other regions after ischemia. Tat-SH3GL2 treatment in gerbils appreciably improved ischemia-induced hyperactivity 1 day after ischemia and the percentage of NeuN-immunoreactive surviving cells increased 4 days after ischemia. In addition, Tat-SH3GL2 treatment in gerbils alleviated the increase in lipid peroxidation as assessed by the levels of malondialdehyde and 8-iso-prostaglandin F2α and in pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, and interleukin-6; while the reduction of protein levels in markers for synaptic plasticity, such as postsynaptic density 95, synaptophysin, and synaptosome associated protein 25 after transient forebrain ischemia was also observed. These results suggest that Tat-SH3GL2 protects neurons from oxidative and ischemic damage by reducing lipid peroxidation and inflammation and improving synaptic plasticity after ischemia.

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Endophilin A1 Promotes Actin Polymerization in Dendritic Spines Required for Synaptic Potentiation

Cited by 20 publications

References 55 publications

Anterograde Viral Tracer Herpes Simplex Virus 1 Strain H129 Transports Primarily as Capsids in Cortical Neuron Axons

Anterograde Viral Tracer Herpes Simplex Virus 1 Strain H129 Transports Primarily as Capsids in Cortical Neuron Axons

BAR domain proteins—a linkage between cellular membranes, signaling pathways, and the actin cytoskeleton

Tat-Endophilin A1 Fusion Protein Protects Neurons from Ischemic Damage in the Gerbil Hippocampus: A Possible Mechanism of Lipid Peroxidation and Neuroinflammation Mitigation as Well as Synaptic Plasticity

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