Proteomic Profiling of Purkinje Cell Surface Reveals the Critical Role of Armadillo-like helical domain containing protein 4 in Mammalian Dendrite Morphogenesis
Abstract/Contents
- Abstract
- Improper dendrite development is exhibited in a range of human neurodevelopmental disorders and neurodegenerative diseases, such as autism spectrum disorder and schizophrenia. Yet, the underlying molecular mechanisms of dendrite morphogenesis are not well characterized. During neuronal development, highly conserved, precisely timed protein interactions at the cell surface mediate dendrite morphogenesis; therefore, cell surface protein identification and characterization may provide key insights to the intricate molecular processes essential to proper dendrite development. Using cell surface proteomic datasets attained by a novel spatiotemporally resolved proteomic profiling technique in situ, we instructed a loss-of-function candidate screen of 13 cell surface proteins to observe their impacts on dendrite morphology. We found that in vivo disruption of the transmembrane protein Armadillo-like helical domain-containing protein 4 (Armh4) engendered a striking dendrite morphological phenotype in transfected cerebellar Purkinje cells. Armh4 disrupted cells exhibited significant height deficiency, decreased total dendrite length and branching, and growth of additional primary dendrites. Here, we present the critical cell-autonomous function and characterization of the signaling mechanisms of the Purkinje cell surface protein Armadillo-like helical domain containing protein 4 (Armh4) during dendrite morphogenesis. We demonstrate that dendrite morphogenesis is sensitive to Armh4 cell surface levels and that endocytosis is required for Armh4 signaling downregulation in proper dendrite development.
Description
| Type of resource | text |
|---|---|
| Date modified | December 5, 2022 |
| Publication date | May 6, 2022; May 2022 |
Creators/Contributors
| Author | Sinantha-Hu, Miley |
https://orcid.org/0000-0002-4901-8821
(unverified)
|
|---|---|---|
| Thesis advisor | McConnell, Susan K |
https://orcid.org/0000-0003-0668-9569
(unverified)
|
| Thesis advisor | Luo, Liqun |
https://orcid.org/0000-0001-5467-9264
(unverified)
|
| Degree granting institution | Stanford University, Department of Biology |
Subjects
| Subject | Biology |
|---|---|
| Subject | Molecular biology |
| Subject | Genetics |
| Subject | Proteomics |
| Subject | Morphogenesis |
| Subject | Developmental biology |
| Subject | Neurodevelopment |
| Subject | Dendrites |
| Genre | Text |
| Genre | Thesis |
Bibliographic information
| Related item | |
|---|---|
| DOI | https://doi.org/10.25740/mv972js5229 |
| Location | https://purl.stanford.edu/mv972js5229 |
Access conditions
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 4.0 International license (CC BY-NC).
Preferred citation
- Preferred citation
- Sinantha-Hu, M. (2023). Proteomic Profiling of Purkinje Cell Surface Reveals the Critical Role of Armadillo-like helical domain containing protein 4 in Mammalian Dendrite Morphogenesis. Stanford Digital Repository. Available at https://purl.stanford.edu/mv972js5229
Collection
Undergraduate Theses, Department of Biology, 2021-2022
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