An Input-Specific Orphan Receptor GPR158-HSPG Interaction Organizes Hippocampal Mossy Fiber-CA3 Synapses

Giuseppe Condomitti, Keimpe D. Wierda, Anna Schroeder, Sara E. Rubio, Kristel M. Vennekens, Cesare Orlandi, Kirill A. Martemyanov, Natalia V. Gounko, Jeffrey Nicholas Savas, Joris de Wit*

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Pyramidal neuron dendrites integrate synaptic input from multiple partners. Different inputs converging on the same dendrite have distinct structural and functional features, but the molecular mechanisms organizing input-specific properties are poorly understood. We identify the orphan receptor GPR158 as a binding partner for the heparan sulfate proteoglycan (HSPG) glypican 4 (GPC4). GPC4 is enriched on hippocampal granule cell axons (mossy fibers), whereas postsynaptic GPR158 is restricted to the proximal segment of CA3 apical dendrites receiving mossy fiber input. GPR158-induced presynaptic differentiation in contacting axons requires cell-surface GPC4 and the co-receptor LAR. Loss of GPR158 increases mossy fiber synapse density but disrupts bouton morphology, impairs ultrastructural organization of active zone and postsynaptic density, and reduces synaptic strength of this connection, while adjacent inputs on the same dendrite are unaffected. Our work identifies an input-specific HSPG-GPR158 interaction that selectively organizes synaptic architecture and function of developing mossy fiber-CA3 synapses in the hippocampus. The molecular mechanisms by which pyramidal neurons organize the structural and functional properties of their synaptic inputs are poorly understood. Condomitti et al. identify an input-specific orphan receptor GPR158-HSPG interaction that selectively organizes mossy fiber inputs onto CA3 pyramidal neurons.

Original languageEnglish (US)
Pages (from-to)201-215.e9
JournalNeuron
Volume100
Issue number1
DOIs
StatePublished - Oct 10 2018

Fingerprint

Hippocampal Mossy Fibers
Heparan Sulfate Proteoglycans
Glypicans
Dendrites
Synapses
Pyramidal Cells
Axons
Post-Synaptic Density
Sexual Partners
Hippocampus

Keywords

  • active zone
  • glutamatergic transmission
  • heparan sulfate proteoglycan
  • hippocampus
  • mossy fiber synapse
  • orphan receptor
  • postsynaptic density
  • pyramidal neuron
  • synaptic specificity
  • synaptogenesis

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Condomitti, G., Wierda, K. D., Schroeder, A., Rubio, S. E., Vennekens, K. M., Orlandi, C., ... de Wit, J. (2018). An Input-Specific Orphan Receptor GPR158-HSPG Interaction Organizes Hippocampal Mossy Fiber-CA3 Synapses. Neuron, 100(1), 201-215.e9. https://doi.org/10.1016/j.neuron.2018.08.038
Condomitti, Giuseppe ; Wierda, Keimpe D. ; Schroeder, Anna ; Rubio, Sara E. ; Vennekens, Kristel M. ; Orlandi, Cesare ; Martemyanov, Kirill A. ; Gounko, Natalia V. ; Savas, Jeffrey Nicholas ; de Wit, Joris. / An Input-Specific Orphan Receptor GPR158-HSPG Interaction Organizes Hippocampal Mossy Fiber-CA3 Synapses. In: Neuron. 2018 ; Vol. 100, No. 1. pp. 201-215.e9.
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Condomitti, G, Wierda, KD, Schroeder, A, Rubio, SE, Vennekens, KM, Orlandi, C, Martemyanov, KA, Gounko, NV, Savas, JN & de Wit, J 2018, 'An Input-Specific Orphan Receptor GPR158-HSPG Interaction Organizes Hippocampal Mossy Fiber-CA3 Synapses', Neuron, vol. 100, no. 1, pp. 201-215.e9. https://doi.org/10.1016/j.neuron.2018.08.038

An Input-Specific Orphan Receptor GPR158-HSPG Interaction Organizes Hippocampal Mossy Fiber-CA3 Synapses. / Condomitti, Giuseppe; Wierda, Keimpe D.; Schroeder, Anna; Rubio, Sara E.; Vennekens, Kristel M.; Orlandi, Cesare; Martemyanov, Kirill A.; Gounko, Natalia V.; Savas, Jeffrey Nicholas; de Wit, Joris.

In: Neuron, Vol. 100, No. 1, 10.10.2018, p. 201-215.e9.

Research output: Contribution to journalArticle

TY - JOUR

T1 - An Input-Specific Orphan Receptor GPR158-HSPG Interaction Organizes Hippocampal Mossy Fiber-CA3 Synapses

AU - Condomitti, Giuseppe

AU - Wierda, Keimpe D.

AU - Schroeder, Anna

AU - Rubio, Sara E.

AU - Vennekens, Kristel M.

AU - Orlandi, Cesare

AU - Martemyanov, Kirill A.

AU - Gounko, Natalia V.

AU - Savas, Jeffrey Nicholas

AU - de Wit, Joris

PY - 2018/10/10

Y1 - 2018/10/10

N2 - Pyramidal neuron dendrites integrate synaptic input from multiple partners. Different inputs converging on the same dendrite have distinct structural and functional features, but the molecular mechanisms organizing input-specific properties are poorly understood. We identify the orphan receptor GPR158 as a binding partner for the heparan sulfate proteoglycan (HSPG) glypican 4 (GPC4). GPC4 is enriched on hippocampal granule cell axons (mossy fibers), whereas postsynaptic GPR158 is restricted to the proximal segment of CA3 apical dendrites receiving mossy fiber input. GPR158-induced presynaptic differentiation in contacting axons requires cell-surface GPC4 and the co-receptor LAR. Loss of GPR158 increases mossy fiber synapse density but disrupts bouton morphology, impairs ultrastructural organization of active zone and postsynaptic density, and reduces synaptic strength of this connection, while adjacent inputs on the same dendrite are unaffected. Our work identifies an input-specific HSPG-GPR158 interaction that selectively organizes synaptic architecture and function of developing mossy fiber-CA3 synapses in the hippocampus. The molecular mechanisms by which pyramidal neurons organize the structural and functional properties of their synaptic inputs are poorly understood. Condomitti et al. identify an input-specific orphan receptor GPR158-HSPG interaction that selectively organizes mossy fiber inputs onto CA3 pyramidal neurons.

AB - Pyramidal neuron dendrites integrate synaptic input from multiple partners. Different inputs converging on the same dendrite have distinct structural and functional features, but the molecular mechanisms organizing input-specific properties are poorly understood. We identify the orphan receptor GPR158 as a binding partner for the heparan sulfate proteoglycan (HSPG) glypican 4 (GPC4). GPC4 is enriched on hippocampal granule cell axons (mossy fibers), whereas postsynaptic GPR158 is restricted to the proximal segment of CA3 apical dendrites receiving mossy fiber input. GPR158-induced presynaptic differentiation in contacting axons requires cell-surface GPC4 and the co-receptor LAR. Loss of GPR158 increases mossy fiber synapse density but disrupts bouton morphology, impairs ultrastructural organization of active zone and postsynaptic density, and reduces synaptic strength of this connection, while adjacent inputs on the same dendrite are unaffected. Our work identifies an input-specific HSPG-GPR158 interaction that selectively organizes synaptic architecture and function of developing mossy fiber-CA3 synapses in the hippocampus. The molecular mechanisms by which pyramidal neurons organize the structural and functional properties of their synaptic inputs are poorly understood. Condomitti et al. identify an input-specific orphan receptor GPR158-HSPG interaction that selectively organizes mossy fiber inputs onto CA3 pyramidal neurons.

KW - active zone

KW - glutamatergic transmission

KW - heparan sulfate proteoglycan

KW - hippocampus

KW - mossy fiber synapse

KW - orphan receptor

KW - postsynaptic density

KW - pyramidal neuron

KW - synaptic specificity

KW - synaptogenesis

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DO - 10.1016/j.neuron.2018.08.038

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JO - Neuron

JF - Neuron

SN - 0896-6273

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Condomitti G, Wierda KD, Schroeder A, Rubio SE, Vennekens KM, Orlandi C et al. An Input-Specific Orphan Receptor GPR158-HSPG Interaction Organizes Hippocampal Mossy Fiber-CA3 Synapses. Neuron. 2018 Oct 10;100(1):201-215.e9. https://doi.org/10.1016/j.neuron.2018.08.038