Arc Oligomerization Is Regulated by CaMKII Phosphorylation of the GAG Domain: An Essential Mechanism for Plasticity and Memory Formation

Zhang, Wenchi; Chuang, Ying Ji; Na, Youn; Ye, Zengyou; Yang, Liuqing; Lin, Raozhou; Zhou, Jiechao; Wu, Jing; Qiu, Jessica; Savonenko, Alena; Leahy, Daniel J.; Huganir, Richard L.; Linden, David J.; Worley, Paul F.

doi:10.1016/j.molcel.2019.05.004

Cited by 36 publications

(71 citation statements)

References 52 publications

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“…S5A-B), though the linker connecting CANTD and CACTD is more rigid in monomeric rArc. The protein-protein interfaces in the dArc capsid do not correspond to those predicted based on rArc crystal contacts (Zhang et al, 2019). The dArc extended N-terminal chain (dArc1 residues 42-55, dArc2 residues 29-32) binds into, and occludes, a hydrophobic groove between a1 and the linker between a2 and a3 ( Fig.…”

Section: Introductionmentioning

confidence: 90%

Structures of virus-like capsids formed by the Drosophila neuronal Arc proteins

Erlendsson

Morado

Shepherd

et al. 2019

Preprint

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The neuronal protein Arc is a critical mediator of synaptic plasticity. Arc originated in tetrapods and flies through domestication of retrotransposon Gag genes. Recent studies have suggested that Arc mediates intercellular mRNA transfer and like Gag, can form capsid-like structures. Here we report that Drosophila proteins dArc1 and dArc2 assemble virus-like capsids. We determine the capsid structures to 2.8 Å and 3.7 Å resolution, respectively, finding similarity to capsids of retroviruses and retrotransposons. Differences between dArc1 and dArc2 capsids, including the presence of a structured zinc-finger pair in dArc1, are consistent with differential RNA-binding specificity. Our data support a model in which ancestral capsid-forming and RNA-binding properties of Arc remain under positive selection pressure and have been repurposed to function in neuronal signalling.

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Section: Introductionmentioning

confidence: 90%

Structures of virus-like capsids formed by the Drosophila neuronal Arc proteins

Erlendsson

Morado

Shepherd

et al. 2019

Preprint

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“…Expression of the cytoskeleton‐associated immediate early gene Arc is rapidly induced by neuronal activity to participate in various forms of synaptic plasticity, including LTP, LTD and homeostatic scaling (Carmichael & Henley, 2018). It plays pivotal roles in regulating AMPAR trafficking (Chowdhury et al., 2006; Shepherd et al., 2006), memory formation (Zhang et al., 2019) and trafficking of the Alzheimer's associated proteins amyloid precursor protein and beta‐site amyloid precursor protein cleaving enzyme 1 (β‐secretase 1) (Wu et al, 2011).…”

Section: Sumoylation Of Other Proteins Involved In the Regulation Of mentioning

confidence: 99%

SUMOylation of synaptic and synapse‐associated proteins: An update

Henley

Seager

Nakamura

et al. 2020

Journal of Neurochemistry

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SUMOylation is a post‐translational modification that regulates protein signalling and complex formation by adjusting the conformation or protein–protein interactions of the substrate protein. There is a compelling and rapidly expanding body of evidence that, in addition to SUMOylation of nuclear proteins, SUMOylation of extranuclear proteins contributes to the control of neuronal development, neuronal stress responses and synaptic transmission and plasticity. In this brief review we provide an update of recent developments in the identification of synaptic and synapse‐associated SUMO target proteins and discuss the cell biological and functional implications of these discoveries.

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“…Without its N-terminal domain, mArc is monomeric in solution [17]. In mArc, it is likely that the presence of both mArc-NT and mArc-CT are required for high-order oligomerization and capsid formation [18,19].…”

Section: Introductionmentioning

confidence: 99%

Crystal and solution structures reveal oligomerization of individual capsid homology domains of Drosophila Arc

Hallin

Markússon

Böttger

et al. 2020

Preprint

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Synaptic plasticity is vital for brain function and memory formation. One of the key proteins in long-term synaptic plasticity and memory is the activity-regulated cytoskeleton-associated protein (Arc). Mammalian Arc forms virus-like capsid-like structures in a process requiring the N-terminal domain and contains two C-terminal lobes that are structural homologues to retroviral capsids. Drosophila has two isoforms of Arc, dArc1 and dArc2, with low sequence similarity to mammalian Arc, but lacking the mammalian Arc N-terminal domain. Both dArc isoforms have a capsid homology domain consisting of N- and C-terminal lobes. We carried out structural characterization of the four individual dArc lobe domains. As opposed to the corresponding mammalian Arc lobe domains, which are monomeric, the dArc lobes were all oligomeric in solution, indicating a strong propensity for homophilic interactions. The N-lobe from dArc2 formed a domain-swapped dimer in the crystal structure, resulting in a novel dimer interaction that could be relevant for capsid assembly or other dArc functions. This domain-swapped structure resembles the dimeric protein C of flavivirus capsids, as well as the structure of histones dimers, domain-swapped transcription factors, and membrane-interacting BAK domains. The strong oligomerization properties of the isolated dArc lobe domains explain the ability of dArc to form capsids in the absence of any large N-terminal domain, in contrast to the mammalian protein.

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Arc Oligomerization Is Regulated by CaMKII Phosphorylation of the GAG Domain: An Essential Mechanism for Plasticity and Memory Formation

Abstract: Highlights d Arc GAG domain is phosphorylated by CaMKII, which prevents Arc oligomerization d Arc phosphorylation controls the magnitude of mGluRdependent LTD d Arc regulation by CaMKII phosphorylation is required for adaptive learning

Cited by 36 publications

References 52 publications

Structures of virus-like capsids formed by the Drosophila neuronal Arc proteins

Structures of virus-like capsids formed by the Drosophila neuronal Arc proteins

SUMOylation of synaptic and synapse‐associated proteins: An update

Crystal and solution structures reveal oligomerization of individual capsid homology domains of Drosophila Arc

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