Candidate Retrograde Signaling Molecules

Physical Coupling {i.e., Integrins)

Physical Coupling {i.e., Integrins)

BOX 2 Potential mechanisms for retrograde signaling.

connect with a partner molecule on an adjacent cell, which also crosses its cell membrane. Thus, they connect the cyto-plasmic compartments of two cells. In addition, signal transduction by these molecules is a two-way street—cytoplasmic domain conformational changes can be transferred to the extracellular domain of the same molecule, which is linked to its partner in the adjacent cell. We will return to some specific candidates in this category for retrograde signaling in Chapter 6.

side. Several groups found evidence for postsynaptic changes that could account for the apparently presynaptic changes identified by quantal analysis studies. Specifically, evidence was generated for what are termed silent synapses (see Box 3). These are synapses that contain NMDA receptors but no AMPA receptors— they are capable of synaptic plasticity mediated by NMDA receptor activation but are physiologically silent in terms of baseline synaptic transmission. Silent synapses are rendered active by NMDA

receptor-triggered activation of latent AMPA receptors postsynaptically. Such an uncovering of silent AMPA receptors could involve membrane insertion or post-translational activation of already-inserted receptors. Activation of silent synapses is a postsynaptic mechanism that could explain the effects (decreased failure rate, for example) in quantal analysis experiments that implied presynaptic changes. Thus, there is now an argument that all of LTP physiology and biochemistry could be postsynaptic.

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