TABLE 1.

Comparison of CAMs that undergo activity-dependent proteolytic cleavage and what the cleaved fragments do at the synapse during development and adulthood. Here we list molecules that undergo activity-dependent cleavage, the type of activity that has been shown to cleave them, and the protease(s) responsible for this cleavage. The possible roles of cleaved proteins during development versus adulthood are also compared.

Family	Molecule	Types of activity	Developmental function(s)	Adult function(s)	Protease(s)	Reference
Transmembrane protein
SIRP	SIRPα	Glutamate receptor activation, depolarization	Cleaved ectodomain drives presynaptic maturation	Unknown	MMP	Umemori & Sanes, 2008, Toth et al., 2013
Neuroligin	Neuroligin-1	Glutamate receptor activation, seizures, light exposure, depolarization	Decrease in neurotransmitter release probability	Synaptic homeostasis?	MMP-9, ADAM-10	Suzuki et al., 2012; Peixoto et al., 2012
	Neuroligin-3	Optogenetic stimulation	Unknown	Unknown	Unknown	Venkatesh et al., 2015
Cadherin	N-Cadherin	NMDA receptor activation	Unknown	LTP? Regulation of spine size?	MMP-9, ADAM-10	Reiss et al., 2005, Uemura et al., 2006
ICAM	ICAM-5	Glutamate receptor activation, seizures, LTP	Cleavage permits postsynaptic maturation	LTP? AMPAR membrane insertion?	MMP-2, MMP-9	Tian et al., 2007; Conant et al. 2010, Lonskaya et al., 2013
SynCAM	SynCAM-2	Unknown	Unknown	Unknown	MMP-9	Tanabe et al., 2008, Bajor et al., 2012
Nectin	Nectin-1	NMDA receptor activation	Unknown	Spine maintenance	ADAM-10	Kim et al., 2010, Lim et al., 2012
	Nectin-3	NMDA receptor activation, Chronic stress	Unknown	Unknown	MMP-9	van der Kooij et al., 2014
APP	APP	Varied	Unknown	Hebbian plasticity	α-secretase	Kamenetz et al., 2003, Hsieh et al., 2006, Shankar et al., 2008
Dystroglycan	β-Dystroglycan	Glutamate receptor activation, seizures	Unknown	Unknown	MMP-9	Michaluk et al., 2007, Dziembowska et al., 2012
NCAM	NCAM	LTP induction	Cleaved fragment decreases excitatory synapse number	Unknown	MMP-9	Fazeli et al., 1994, Pillai-Nair et al., 2005, Hinkle et al., 2006
L1-CAM	L1-CAM	NMDA receptor activation	Unknown	LTP?	Neuropsin	Matsumoto-Miyai et al., 2003
Netrin Ligand	G-NGL-3	LTD induction	Unknown	Unknown	MMP	Lee et al., 2014
Neurexin	Neurexin-3β	Glutamate receptor activation, depolarization	Unknown	Unknown	α-secretase	Bot et al., 2011, Saura et al., 2011
Extracellular matrix proteins
Collagen	Multiplexin (Drosophila)	Glutamate receptor suppression	Unknown	Homeostatic plasticity	Unknown	Wang et al., 2014
Agrin	Agrin	Concurrent activation of pre & postsynaptic terminals	Unknown	Formation of dendritic filopodia	Neurotrypsin	Matsumoto-Miyai et al., 2009