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Teneurins instruct synaptic partner matching in an olfactory map.

Hong W, Mosca TJ, Luo L - Nature (2012)

Bottom Line: Ten-m and Ten-a are highly expressed in select PN-ORN matching pairs.Teneurin loss- and gain-of-function cause specific mismatching of select ORNs and PNs.We propose that Teneurins instruct matching specificity between synaptic partners through homophilic attraction.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.

ABSTRACT
Neurons are interconnected with extraordinary precision to assemble a functional nervous system. Compared to axon guidance, far less is understood about how individual pre- and postsynaptic partners are matched. To ensure the proper relay of olfactory information in the fruitfly Drosophila, axons of ∼50 classes of olfactory receptor neurons (ORNs) form one-to-one connections with dendrites of ∼50 classes of projection neurons (PNs). Here, using genetic screens, we identified two evolutionarily conserved, epidermal growth factor (EGF)-repeat containing transmembrane Teneurin proteins, Ten-m and Ten-a, as synaptic-partner-matching molecules between PN dendrites and ORN axons. Ten-m and Ten-a are highly expressed in select PN-ORN matching pairs. Teneurin loss- and gain-of-function cause specific mismatching of select ORNs and PNs. Finally, Teneurins promote homophilic interactions in vitro, and Ten-m co-expression in non-partner PNs and ORNs promotes their ectopic connections in vivo. We propose that Teneurins instruct matching specificity between synaptic partners through homophilic attraction.

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Ten-m promotes homophilic interactions in vitro and in vivoa, Co-immunoprecipitation of FLAG- and HA-tagged Teneurins from separately transfected S2 cells. Co-immunoprecipitated HA-tagged Teneurins are detected by anti-HA antibody and immunoprecipitated FLAG-tagged Teneurins by anti-FLAG antibody (upper two blots). The input lysates are immunoblotted for HA and FLAG (lower two blots). b, Schematic showing the relative positions of glomeruli targeted by Mz19 PN dendrites (green) and AM29 ORN axons (red). c, Quantification of mismatching between Mz19 PNs and AM29 ORNs (n=10 for each condition). d, In control, Mz19 dendrites do not connect with AM29 axons. e-f, Overexpression of Ten-m only in AM29 ORNs (e) or Mz19 PNs (f) does not produce mismatching between them. Following Ten-m overexpression, AM29 axons mistarget posteriorly to Mz19 dendrites and are therefore not visible in e. g, Simultaneous overexpression of Ten-m in both PNs and ORNs produces ectopic Mz19-AM29 connections (arrowhead). Schematics on the right show the Mz19-AM29 connectivity in different conditions. h, The synaptic vesicle marker Synaptotagmin is enriched at these Mz19-AM29 ectopic connections. AM29 axons are labeled by AM29-Gal4 with UAS-mtdT to visualize the entire axonal processes and UAS-synaptotagmin-HA to visualize synaptic vesicles in axon terminals. Mz19 dendrites are labeled by Mz19-QF driving QUAS-mCD8GFP.
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Figure 5: Ten-m promotes homophilic interactions in vitro and in vivoa, Co-immunoprecipitation of FLAG- and HA-tagged Teneurins from separately transfected S2 cells. Co-immunoprecipitated HA-tagged Teneurins are detected by anti-HA antibody and immunoprecipitated FLAG-tagged Teneurins by anti-FLAG antibody (upper two blots). The input lysates are immunoblotted for HA and FLAG (lower two blots). b, Schematic showing the relative positions of glomeruli targeted by Mz19 PN dendrites (green) and AM29 ORN axons (red). c, Quantification of mismatching between Mz19 PNs and AM29 ORNs (n=10 for each condition). d, In control, Mz19 dendrites do not connect with AM29 axons. e-f, Overexpression of Ten-m only in AM29 ORNs (e) or Mz19 PNs (f) does not produce mismatching between them. Following Ten-m overexpression, AM29 axons mistarget posteriorly to Mz19 dendrites and are therefore not visible in e. g, Simultaneous overexpression of Ten-m in both PNs and ORNs produces ectopic Mz19-AM29 connections (arrowhead). Schematics on the right show the Mz19-AM29 connectivity in different conditions. h, The synaptic vesicle marker Synaptotagmin is enriched at these Mz19-AM29 ectopic connections. AM29 axons are labeled by AM29-Gal4 with UAS-mtdT to visualize the entire axonal processes and UAS-synaptotagmin-HA to visualize synaptic vesicles in axon terminals. Mz19 dendrites are labeled by Mz19-QF driving QUAS-mCD8GFP.

Mentions: To test whether Teneurins interact in vitro, we separately transfected two populations of Drosophila S2 cells with FLAG- and HA-tagged Teneurins, and performed co-immunoprecipitations from lysates of these cells after mixing. We detected strong homophilic interactions between FLAG- and HA-tagged Ten-m proteins, and to a lesser extent between FLAG- and HA-tagged Ten-a proteins (Fig. 5a). Ten-m and Ten-a alsoexhibited heterophilic interactions (Fig. 5a), which may account for their role in synapse organization26.


Teneurins instruct synaptic partner matching in an olfactory map.

Hong W, Mosca TJ, Luo L - Nature (2012)

Ten-m promotes homophilic interactions in vitro and in vivoa, Co-immunoprecipitation of FLAG- and HA-tagged Teneurins from separately transfected S2 cells. Co-immunoprecipitated HA-tagged Teneurins are detected by anti-HA antibody and immunoprecipitated FLAG-tagged Teneurins by anti-FLAG antibody (upper two blots). The input lysates are immunoblotted for HA and FLAG (lower two blots). b, Schematic showing the relative positions of glomeruli targeted by Mz19 PN dendrites (green) and AM29 ORN axons (red). c, Quantification of mismatching between Mz19 PNs and AM29 ORNs (n=10 for each condition). d, In control, Mz19 dendrites do not connect with AM29 axons. e-f, Overexpression of Ten-m only in AM29 ORNs (e) or Mz19 PNs (f) does not produce mismatching between them. Following Ten-m overexpression, AM29 axons mistarget posteriorly to Mz19 dendrites and are therefore not visible in e. g, Simultaneous overexpression of Ten-m in both PNs and ORNs produces ectopic Mz19-AM29 connections (arrowhead). Schematics on the right show the Mz19-AM29 connectivity in different conditions. h, The synaptic vesicle marker Synaptotagmin is enriched at these Mz19-AM29 ectopic connections. AM29 axons are labeled by AM29-Gal4 with UAS-mtdT to visualize the entire axonal processes and UAS-synaptotagmin-HA to visualize synaptic vesicles in axon terminals. Mz19 dendrites are labeled by Mz19-QF driving QUAS-mCD8GFP.
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Figure 5: Ten-m promotes homophilic interactions in vitro and in vivoa, Co-immunoprecipitation of FLAG- and HA-tagged Teneurins from separately transfected S2 cells. Co-immunoprecipitated HA-tagged Teneurins are detected by anti-HA antibody and immunoprecipitated FLAG-tagged Teneurins by anti-FLAG antibody (upper two blots). The input lysates are immunoblotted for HA and FLAG (lower two blots). b, Schematic showing the relative positions of glomeruli targeted by Mz19 PN dendrites (green) and AM29 ORN axons (red). c, Quantification of mismatching between Mz19 PNs and AM29 ORNs (n=10 for each condition). d, In control, Mz19 dendrites do not connect with AM29 axons. e-f, Overexpression of Ten-m only in AM29 ORNs (e) or Mz19 PNs (f) does not produce mismatching between them. Following Ten-m overexpression, AM29 axons mistarget posteriorly to Mz19 dendrites and are therefore not visible in e. g, Simultaneous overexpression of Ten-m in both PNs and ORNs produces ectopic Mz19-AM29 connections (arrowhead). Schematics on the right show the Mz19-AM29 connectivity in different conditions. h, The synaptic vesicle marker Synaptotagmin is enriched at these Mz19-AM29 ectopic connections. AM29 axons are labeled by AM29-Gal4 with UAS-mtdT to visualize the entire axonal processes and UAS-synaptotagmin-HA to visualize synaptic vesicles in axon terminals. Mz19 dendrites are labeled by Mz19-QF driving QUAS-mCD8GFP.
Mentions: To test whether Teneurins interact in vitro, we separately transfected two populations of Drosophila S2 cells with FLAG- and HA-tagged Teneurins, and performed co-immunoprecipitations from lysates of these cells after mixing. We detected strong homophilic interactions between FLAG- and HA-tagged Ten-m proteins, and to a lesser extent between FLAG- and HA-tagged Ten-a proteins (Fig. 5a). Ten-m and Ten-a alsoexhibited heterophilic interactions (Fig. 5a), which may account for their role in synapse organization26.

Bottom Line: Ten-m and Ten-a are highly expressed in select PN-ORN matching pairs.Teneurin loss- and gain-of-function cause specific mismatching of select ORNs and PNs.We propose that Teneurins instruct matching specificity between synaptic partners through homophilic attraction.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.

ABSTRACT
Neurons are interconnected with extraordinary precision to assemble a functional nervous system. Compared to axon guidance, far less is understood about how individual pre- and postsynaptic partners are matched. To ensure the proper relay of olfactory information in the fruitfly Drosophila, axons of ∼50 classes of olfactory receptor neurons (ORNs) form one-to-one connections with dendrites of ∼50 classes of projection neurons (PNs). Here, using genetic screens, we identified two evolutionarily conserved, epidermal growth factor (EGF)-repeat containing transmembrane Teneurin proteins, Ten-m and Ten-a, as synaptic-partner-matching molecules between PN dendrites and ORN axons. Ten-m and Ten-a are highly expressed in select PN-ORN matching pairs. Teneurin loss- and gain-of-function cause specific mismatching of select ORNs and PNs. Finally, Teneurins promote homophilic interactions in vitro, and Ten-m co-expression in non-partner PNs and ORNs promotes their ectopic connections in vivo. We propose that Teneurins instruct matching specificity between synaptic partners through homophilic attraction.

Show MeSH
Related in: MedlinePlus