Cell Death Differ: The interaction between Hevin and calcyon can promote synaptic reorganization after brain injury

Recovery after brain injury is a multi-step process, including tissue remodeling, synaptic reorganization, and functional plasticity.
Synapse reorganization is a form of brain plasticity, including the formation of new circuits composed of excitatory and inhibitory neurons.

Although the reorganization of synapses depends on the connections between neuronal cells, in the past few decades, astrocytes have been considered as the third key component of synapses, and it has been confirmed that they are structurally important.
A key role in synapse formation.

Hevin, also known as SPARC-like protein 1 (SPARCL1 or SC1), is a synaptic protein secreted by astrocytes, which can interact with synaptic adhesion proteins (such as neurotoxins and glial proteins).
To regulate the formation of glutamatergic synapses during brain development.

In this study, the researchers determined that the neuron-specific vesicle protein calcyon is a new type of interaction protein of hevin, and confirmed that this interaction plays a key role in the reorganization of synapses after mature brain injury.
In the thrombotic stroke model, the researchers found that the level of hevin in astrocytes after injury was up-regulated.

Spatiotemporal expressions of hevin and synaptophysin in the sensory motor cortex after brain injury

In the acute phase of brain injury, Hevin can be fragmented by MMP3 induced by brain injury, which is related to severe gliosis.
In the late stage of brain injury, as the expression level of MMP3 decreases, the level of functional Hevin is restored.

The researchers found that the C-terminus of hevin can interact with the N-terminus of calcyon.
By using RNAi and binding competitive peptides in a model of ischemic brain injury, and based on histological and electrophysiological analysis, the researchers found that this interaction is crucial in the recovery of synaptic function in the sensorimotor cortex.

Hevin interacts with calcyon

All in all, the results of this study reveal a causal relationship between the interaction between hevin and calcyon and synaptic reorganization after brain injury.
This neuron-glia interaction can be used to regulate synaptic reorganization under various nervous system conditions.

Original source:

Kim, JH.
, Jung, HG.
, Kim, A.