Synaptic functions of latrophilins and teneurins
Abstract/Contents
- Abstract
- The synapse is the fundamental unit of the brain that enables information processing within circuits of interconnected neurons. The molecular mechanisms of synapse formation and function are critical for brain development and function, in health and in disease. Synaptic cell-adhesion is an essential feature of synapses that has been shown to regulate synapse number, control synaptic properties and affect downstream behaviors. Careful study of the molecular participants in synaptic cell-adhesion and how they work to specify and regulate synapses is needed to reach a molecular-level understanding of the synapses underlying particular circuits and behaviors and may lead the way to novel therapeutic approaches for brain disorders. The latrophilins (Lphns) and teneurins (Tens) are two families of cell-adhesion molecules that are expressed at synapses and interact in a trans- conformation. The latrophilin isoforms Lphn2 and Lphn3 have been shown to be postsynaptic regulators of excitatory synapse number and transmission in mouse hippocampus that function in an input-specific manner, while various Ten orthologs have been shown to be important for proper axonal targeting and are capable of inducing postsynaptic structures in vitro. These data suggest that the latrophilin-teneurin interaction may be a critical mechanism underlying synapse formation and function, however much remains to be learned about how latrophilins and teneurins function at synapses. First, it is unclear if the principles of latrophilin function identified in the hippocampus hold true in other neurons and brain regions that exhibit different patterns of latrophilin expression. In addition, no rigorous studies of teneurin function at synapses in vivo have been performed to date. Finally, there is only limited evidence that latrophilins and teneurins act together to control synapse number and/or function from experiments performed at the same synapses in vivo. This dissertation will cover my progress in dissecting the functions of latrophilins and teneurins at synapses. In Chapter 1, I review in detail the importance of studying the molecular code of synaptic cell-adhesion and the literature to date on latrophilins and teneurins. In Chapter 2, I present a study of the functions of Lphn2 and Lphn3 at Purkinje cell synapses in the cerebellum, where I characterize the expression of Lphns in cerebellum and demonstrate that Lphn2/3 are redundant but essential for parallel-fiber synapse number and synaptic transmission. In Chapter 3, I detail introductory work dissecting the function of Ten3 at synapses between proximal CA1 to distal subiculum neurons, where I find that postsynaptic Ten3 in distal subiculum neurons is not important for maintenance of synaptic strength at synapses from proximal CA1. Taken together, this work expands on our understanding of latrophilins and teneurins as critical mediators of synapse number and function
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2020; ©2020 |
| Publication date | 2020; 2020 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Zhang, Roger Shen |
|---|---|
| Degree supervisor | Südhof, Thomas C |
| Thesis advisor | Südhof, Thomas C |
| Thesis advisor | Chen, Lu, (Professor of neurosurgery) |
| Thesis advisor | Ding, Jun (Jun B.) |
| Degree committee member | Chen, Lu, (Professor of neurosurgery) |
| Degree committee member | Ding, Jun (Jun B.) |
| Associated with | Stanford University, Department of Molecular and Cellular Physiology. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Roger Shen Zhang |
|---|---|
| Note | Submitted to the Department of Molecular and Cellular Physiology |
| Thesis | Thesis Ph.D. Stanford University 2020 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2020 by Roger Shen Zhang
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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