| SHRM3 |
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| Symbol | SHRM3 |
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| Full Name | Shroom Family Member 3 |
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| Chromosome | 19q13.42 |
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| NCBI Gene ID | [63967](https://www.ncbi.nlm.nih.gov/gene/63967) |
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| OMIM | [610595](https://www.omim.org/entry/610595) |
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| Ensembl | [ENSG00000104892](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000104892) |
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| UniProt | [Q9NWB5](https://www.uniprot.org/uniprot/Q9NWB5) |
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| Associated Diseases | [Alzheimer's disease](/diseases/alzheimers-disease), [Parkinson's disease](/diseases/parkinsons-disease), [Neural tube defects](/diseases/neural-tube-defects) |
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SHRM3 (Shroom Family Member 3), also known as Shroom3, is an actin-binding protein that plays critical roles in cellular morphogenesis and tissue development simic2018. Originally identified for its essential function in neural tube closure, SHRM3 regulates apical constriction through direct binding to non-muscle myosin II and the actin cytoskeleton riedl2008.
The Shroom family consists of four members (SHRM1-4) that share conserved domains involved in actin binding and regulation. SHRM3 is expressed in both developing and adult tissues, with particularly high expression in the nervous system and kidney hatano2020. While primarily studied in developmental contexts, SHRM3's role in actin dynamics has significant implications for synaptic plasticity and neurodegenerative diseases pollard2017.
¶ Gene and Protein Structure
The SHRM3 gene is located on chromosome 19q13.42 and encodes a protein of 1934 amino acids with a molecular weight of approximately 210 kDa. The gene contains multiple exons and undergoes alternative splicing to produce variant isoforms.
¶ Protein Domains
SHRM3 contains several functional domains dos Remedios2015:
- N-terminal Shroom domain (ASD): Apical surface-binding domain essential for subcellular localization
- Central region: Contains binding sites for actin and myosin
- PDZ-binding motif: Mediates interactions with PDZ domain-containing proteins
- C-terminal actin-binding domain: Direct interaction with actin filaments
flowchart TD
A["SHRM3"] --> B["Non-muscle Myosin II"]
A --> C["Actin Filaments"]
A --> D["F-actin"]
A --> E["Rho-associated kinases"]
A --> F["ZO-1"]
B --> G["Apical Constriction"]
C --> G
D --> G
SHRM3 is a master regulator of apical constriction zagora2020, a fundamental process in tissue morphogenesis:
- Membrane recruitment: SHRM3 localizes to the apical surface of epithelial cells
- Actin-myosin recruitment: Recruits actin filaments and non-muscle myosin II
- Contractile apparatus: Forms a contractile ring at the apical domain
- Tissue bending: Generates forces that drive tissue invagination
During embryogenesis, SHRM3 is essential for neural tube closure shen2019, ek2010:
- Neural plate bending: Initiates folding of the neural plate
- Neural fold elevation: Promotes elevation of neural folds
- Fusion of folds: Facilitates closure at the midline
- Spina bifida prevention: Proper SHRM3 function prevents neural tube defects
SHRM3 modulates the actin cytoskeleton through multiple mechanisms kalman2018:
- F-actin bundling: Organizes actin filaments into parallel bundles
- Actin polymerization: Regulates actin dynamics
- Cell shape control: Controls epithelial cell morphology
- Tissue integrity: Maintains tissue architecture
SHRM3 plays important roles in synaptic function pollard2017, morita2019:
- Spine morphology: Regulates spine shape and size
- Actin dynamics: Controls spine actin cytoskeleton
- Plasticity mechanisms: Involved in LTP and LTD
- Receptor trafficking: May affect AMPA and NMDA receptor localization
- Post-synaptic density: Localizes to synaptic complexes
- Signal transduction: Interfaces with synaptic signaling pathways
- Neuromuscular junctions: Important for peripheral synapses
- Axon guidance: May influence axonal pathfinding
- Dendritic arborization: Regulates dendrite branching
- Synapse formation: Contributes to synaptogenesis
Actin cytoskeletal alterations are early events in AD pathogenesis halabi2021:
- Dendritic spine loss: Actin dysfunction contributes to spine elimination
- Tau pathology: Tau affects actin-binding proteins
- Synaptic failure: Actin dynamics are disrupted in early AD
- Amyloid effects: Aβ alters actin cytoskeleton
SHRM3 may be affected through:
- Altered expression in AD brain
- Dysregulated actin signaling
- Impaired spine plasticity
Actin cytoskeletal changes also contribute to Parkinson's disease boehm2021:
- Dendritic complexity: Loss of dopaminergic neuron dendrites
- Axonal transport: Actin-based transport disruption
- Synaptic dysfunction: Dopamine release abnormalities
- Lewy body formation: Cytoskeletal components in inclusions
Cytoskeletal abnormalities are prominent in ALS yang2017:
- Motor neuron cytoskeleton: Disrupted actin/microtubule networks
- Axonal transport: Cargo movement impaired
- Synaptic terminals: Nerve terminal dysfunction
SHRM3 mutations are associated with neural tube defects steghaus2020:
- Spina bifida: Failure of spinal cord closure
- Anencephaly: Absence of cranial structures
- Encephalocele: Protrusion of brain tissue
- Renal hypoplasia: Reduced kidney development
- Congenital kidney anomalies: Structural abnormalities
While not directly causative, SHRM3 may contribute to:
- Age-related neurodegeneration
- Synaptic failure in disease
- Cytoskeletal dysfunction
SHRM3 shows distinct expression patterns:
- Kidney: High expression in renal tubules
- Brain: Cortex, cerebellum, hippocampus
- Lung: Bronchial epithelium
- Intestine: Epithelial cells
- Embryonic tissues: High during development
Within the nervous system:
- Cerebral cortex: Pyramidal neurons
- Hippocampus: CA1-CA3 regions, dentate gyrus
- Cerebellum: Purkinje cells
- Spinal cord: Motor neurons
- Neurons: Expression in excitatory and inhibitory neurons
- Astrocytes: Lower expression
- Epithelial cells: High in transporting epithelia
- Endothelial cells: Moderate expression
Modulating SHRM3 function offers therapeutic potential kalman2018:
- Small molecule modulators: Target SHRM3-actin interactions
- Peptide inhibitors: Block protein-protein interactions
- Gene therapy: Modulate SHRM3 expression
- Myosin II inhibitors: Affect downstream effectors
- Actin polymerization modulators: Control actin dynamics
- Rho kinase inhibitors: Affect upstream signaling
- Restore spine plasticity: Enhance actin dynamics
- Protect cytoskeleton: Prevent cytoskeletal breakdown
- Enhance synaptic function: Support synaptic protein interactions
- Axonal transport support: Maintain transport infrastructure
| Challenge |
Approach |
| Protein-protein interactions |
Develop interface inhibitors |
| Cell type specificity |
Target disease-specific isoforms |
| BBB penetration |
Design CNS-penetrant molecules |
| Therapeutic window |
Careful dosing strategies |
- Shrm3 knockout mice: Neural tube defects, embryonic lethal
- Conditional knockouts: Tissue-specific phenotypes
- Transgenic models: Disease-relevant mutations
- Exencephaly
- Spina bifida
- Kidney hypoplasia
- Neuronal functions: Specific roles in different neuron types
- Disease mechanisms: How SHRM3 contributes to neurodegeneration
- Therapeutic targeting: Specific modulators for CNS diseases
- Structural studies: SHRM3-actin complex structures
- Single-cell analysis: Neuron-specific functions
- Organoid models: Brain organoids for disease modeling
- Small molecule development: Brain-penetrant modulators
- SHRM2 — Related Shroom family member
- SHRM4 — Related Shroom family member
- MYH9 — Non-muscle myosin