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Teneurins Are SPARCL1 Receptors
Xuchen Zhang1, Xudong Chen1, Yi Miao1
1Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA.
Biorxiv : the Preprint Server for Biology
|July 29, 2026
Summary
SPARCL1 (Hevin) enhances synapse formation. Its C-terminal domains bind teneurins and activate synapse formation via Ca2+-binding, clarifying its mechanism of action.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- SPARCL1 (Hevin) is a secreted protein involved in synapse formation.
- Its precise mechanism of action at synapses is not fully understood.
- Previous studies show conflicting results regarding SPARCL1's function.
Purpose of the Study:
- To elucidate the specific domains and molecular interactions of SPARCL1 responsible for enhancing synapse formation.
- To clarify the mechanism by which SPARCL1 influences synaptic structure.
Main Methods:
- Utilized cultured neurons from embryonic mice (male and female).
- Investigated the function of SPARCL1's C-terminal domains (follistatin-like and Ca2+-binding).
- Assessed binding affinities to synaptic proteins like neurexins, neuroligins, and teneurins.
Main Results:
- The C-terminal 35% of SPARCL1, including follistatin-like and Ca2+-binding domains, is sufficient for potent synapse enhancement.
- SPARCL1 acts at nanomolar concentrations and avidly interacts with teneurins, but not strongly with neurexin/neuroligin complexes.
- The follistatin-like domain binds teneurins, but only its combination with the Ca2+-binding domain stimulates synapse formation.
Conclusions:
- SPARCL1 enhances synapse numbers by a dual mechanism: binding teneurins via its follistatin-like domain and activating synapse formation via its Ca2+-binding domain.
- This clarifies the functional role of specific SPARCL1 domains in synaptic plasticity and development.
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