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 language | English (US) |
|---|---|
| Pages (from-to) | 201-215.e9 |
| Journal | Neuron |
| Volume | 100 |
| Issue number | 1 |
| DOIs | |
| State | Published - Oct 10 2018 |
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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
}
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 journal › Article
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
UR - http://www.scopus.com/inward/record.url?scp=85053896305&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85053896305&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2018.08.038
DO - 10.1016/j.neuron.2018.08.038
M3 - Article
C2 - 30290982
AN - SCOPUS:85053896305
VL - 100
SP - 201-215.e9
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 1
ER -