Neuronal-specific septin-3 binds Atg8/LC3B, accumulates and localizes to autophagosomes during induced autophagy.
Vilmos TóthHenrietta VadásziLilla RavaszDániel MittliDominik MátyásTamás MolnárAndrás MicsonaiTamás SzaniszlóPéter LőrinczRéka Á KovácsTünde JuhászTamás Beke-SomfaiGábor JuhászBalázs András GyörffyKatalin A KékesiJózsef KardosPublished in: Cellular and molecular life sciences : CMLS (2022)
In synapses that show signs of local apoptosis and mitochondrial stress and undergo neuro-immunological synapse pruning, an increase in the levels of the presynaptic protein, neuronal-specific septin-3 can be observed. Septin-3 is a member of the septin GTPase family with the ability to form multimers and contribute to the cytoskeleton. However, the function of septin-3 remains elusive. Here, we provide evidence that septin-3 is capable of binding the most-studied autophagy protein Atg8 homolog microtubule-associated protein 1 light chain 3B (LC3B), besides another homolog, GABA receptor-associated protein-like 2 (GABARAPL2). Moreover, we demonstrate that colocalization of septin-3 and LC3B increases upon chemical autophagy induction in primary neuronal cells. Septin-3 is accumulated in primary neurons upon autophagy enhancement or blockade, similar to autophagy proteins. Using electron microscopy, we also show that septin-3 localizes to LC3B positive membranes and can be found at mitochondria. However, colocalization results of septin-3 and the early mitophagy marker PTEN-induced kinase 1 (PINK1) do not support that binding of septin-3 to mitochondria is mitophagy related. We conclude that septin-3 correlates with synaptic/neuronal autophagy, binds Atg8 and localizes to autophagic membranes that can be enhanced with chemical autophagy induction. Based on our results, elevated septin-3 levels might indicate enhanced or impeded autophagy in neurons.
Keyphrases
- cell death
- endoplasmic reticulum stress
- oxidative stress
- cell cycle arrest
- induced apoptosis
- signaling pathway
- diabetic rats
- mass spectrometry
- simultaneous determination
- spinal cord injury
- liquid chromatography
- cell proliferation
- spinal cord
- tyrosine kinase
- subarachnoid hemorrhage
- high glucose
- blood brain barrier
- small molecule
- high resolution mass spectrometry