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Updated: Jan 21, 2026

Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain
Published on: August 28, 2012
RIP at the Synapse and the Role of Intracellular Domains in Neurons
Yan Jun Lee1,2, Toh Hean Ch'ng3,4
1Lee Kong Chian School of Medicine, Nanyang Technological University, Clinical Science Building, 11 Mandalay Road, 10-01-01 M, Singapore, 308232, Singapore.
Abstract:
Regulated intramembrane proteolysis (RIP) occurs in a cell when transmembrane proteins are cleaved by intramembrane proteases such as secretases to generate soluble protein fragments in the extracellular environment and the cytosol. In the cytosol, these soluble intracellular domains (ICDs) have local functions near the site of cleavage or in many cases, translocate to the nucleus to modulate gene expression. While the mechanism of RIP is relatively well studied, the fate and function of ICDs for most substrate proteins remain poorly characterized. In neurons, RIP occurs in various subcellular compartments including at the synapse. In this review, we summarize current research on RIP in neurons, focusing specifically on synaptic proteins where the presence and function of the ICDs have been reported. We also briefly discuss activity-driven processing of RIP substrates at the synapse and the cellular machinery that support long-distance transport of ICDs from the synapse to the nucleus. Finally, we describe future challenges in this field of research in the context of understanding the contribution of ICDs in neuronal function.
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