The Synaptojanin 2 Binding Protein (SYNJ2B) exists in the outer mitochondrial membrane and displays critical roles in both nervous system operations and tumor development. SYNJ2B regulates synaptic vesicle cycling which makes it crucial for neuron-to-neuron signal transmission. When SYNJ2B functions abnormally it can cause neuronal damage which results in conditions including motor neuron diseases such as amyotrophic lateral sclerosis (ALS). SYNJ2B expression levels and dysfunction influence the survival and death processes of neurons which subsequently impacts motor neuron health.
SYNJ2B activity influences hepatocyte proliferation and apoptosis as well as their metabolic processes through the regulation of PI3K-Akt signaling pathways and other related signal transduction routes. Research indicates that SYNJ2B could serve as a biomarker for hepatocellular carcinoma while its expression level may correlate with patient outcomes.
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Physiological Activity of SYNJ2BP
Synaptojanin 2 Binding Protein (SYNJ2BP) is a small transmembrane protein located in the outer membrane of mitochondria, with the following physiological characteristics:
Maintenance of mitochondrial function
Participates in regulating the morphology, dynamics and contact of mitochondria with other organelles (such as the endoplasmic reticulum).
Energy metabolism regulation
Supports cellular energy metabolism by maintaining mitochondrial health, especially plays an important role in high-energy demand cells such as neurons.
Cytoprotective effect
Relieves oxidative stress, inhibits the production of reactive oxygen species (ROS), and protects cells from damage caused by metabolic stress and apoptotic signals.
Role of SYNJ2B in Motor Neurons
The outer membrane proteins of mitochondria control cellular metabolic activities while facilitating communication with other organelles including the endoplasmic reticulum. Disruptions at mitochondrial-endoplasmic reticulum contact points (MERCs) can function as a shared pathological mechanism for neurodegenerative diseases. The interruption of MERC function leads to cellular senescence which is a primary risk element for neurodegenerative conditions. SYNJ2BP drives mitochondrial movement along microtubules towards synaptic terminals in motor neurons to deliver necessary energy to nerve terminals. SYNJ2BP preserves neuromuscular junction integrity by ensuring proper mitochondrial function at synapses. Research shows that when SYNJ2BP is missing or not functioning properly it leads to motor neuron degenerative diseases like ALS which indicates its essential role in protecting neurons.
Neural development and function: SYNJ2B helps motor neurons meet their energy requirements and preserves their functionality through the regulation of mitochondrial dynamics including their movement and fusion and fission processes.
Axonal transport: The extended nature of motor neuron axons demands efficient energy supply mechanisms. The distribution and health of mitochondria influenced by SYNJ2B results in improved nerve impulse conduction and neuromuscular junction stability.
Role of SYNJ2B in Hepatocellular Carcinoma (HCC)
Hepatocellular carcinoma represents a major cancer type worldwide while remaining the second primary cancer-related mortality cause. The SYNJ2BP gene which encodes a 145 amino acid protein and resides at location 14q24.2 functions to control Synaptojanin-2 localization while also affecting Activin II receptor endocytosis. The increased expression of SYNJ2BP limits the growth of hepatocellular carcinoma cells such as HepG2 and Huh7 by controlling cell cycle protein levels or triggering apoptosis. The protein SYNJ2BP blocks the movement and invasive characteristics of hepatocellular carcinoma cells through cytoskeletal modification which reduces their capability to metastasize. The anti-tumor effects of SYNJ2BP occur through its negative regulation of cellular proliferation and migration pathways including PI3K/AKT and MAPK.
Inhibition of tumor growth: HCC cell proliferation slows due to SYNJ2B expression which potentially acts through cell metabolism regulation or by triggering apoptosis and cell cycle progression inhibition.
Inhibit tumor metastasis: The metastatic potential of cancer cells decreases when SYNJ2B affects mitochondrial function to limit their migration and invasion capabilities.
Downregulation of SYNJ2BP in Liver Cancer Tissues and Cell Lines
The levels of SYNJ2BP expression showed significant reduction in hepatocellular carcinoma tissues when compared to normal liver tissues. The expression levels of SYNJ2BP mRNA and protein in typical liver cancer cell lines including HepG2 and Huh7 were reduced when compared to normal liver cells. The reduction of SYNJ2BP expression levels might play a role in increasing tumor invasiveness and metastasis. HCC patients with reduced SYNJ2BP expression experience worse outcomes including advanced tumor stages and decreased survival rates. SYNJ2BP could function both as a prognostic biomarker and a therapeutic target.
Possible Mechanisms
- Maintenance of mitochondrial homeostasis: Maintaining mitochondrial function and lowering ROS (reactive oxygen species) production helps to decrease DNA damage along with mutation rates and cancer-promoting pathway activation.
- Energy metabolism regulation: Maintain proper glycolysis and oxidative phosphorylation balance in cancer cells while preventing tumor cells from relying on abnormal energy patterns.
- Signaling pathway effects: This compound may affect key signaling pathways that control tumor growth and metastasis including PI3K/AKT and MAPK.
References
- Verstreken, P., et al. Synaptojanin is recruited by endophilin to promote synaptic vesicle uncoating. Neuron. 2003, 40(4): 733-748.
- Planchart, A., et al. Analysis of an intronic promoter within Synj2. Biochemical and biophysical research communications. 2013, 440(4): 640-645.
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