The emerging roles of Shank3 in cardiac function and dysfunction

Area of Science:

• Neuroscience
• Cardiovascular Biology
• Molecular Biology

Background:

• Shank3 is a crucial scaffold protein in neuronal postsynaptic density (PSD), vital for synaptic function.
• SHANK3 gene mutations are linked to neurodevelopmental disorders like autism spectrum disorders and schizophrenia.
• Emerging evidence suggests Shank3 has roles beyond the brain, including in cardiac tissue.

Purpose of the Study:

• To review current findings on Shank3's role in cardiac function and dysfunction.
• To explore potential molecular mechanisms underlying Shank3's cardiac effects.
• To predict novel functions of Shank3 in the heart based on its known interactors.

Main Methods:

• Review of in vitro and in vivo studies on Shank3.
• Analysis of expression profiling in various tissues and cell types.
• Investigation of Shank3 mutant mouse models for cardiac phenotypes.

Main Results:

• Shank3 interacts with phospholipase Cβ1b (PLCβ1b) in cardiomyocytes, modulating Gq-induced signaling.
• Shank3 mutant mice exhibit altered cardiac morphology and function in models of myocardial infarction and aging.
• Shank3's PSD interactors, also present in the heart, suggest additional cardiac roles.

Conclusions:

• Shank3 is implicated in cardiac function and dysfunction.
• Further research is needed to fully elucidate Shank3's molecular functions in the heart.
• Understanding Shank3's cardiac roles may offer new insights into cardiovascular diseases.