When inserting surface receptors into the somatodendritic plasma membrane, neurons have a choice. Their decision determines how long receptors linger at the point of insertion, as shown by Guillermo Yudowski, Manojkumar Puthenveedu, and Mark von Zastrow (University of California, San Francisco, CA).
The number of receptors in the plasma membrane largely determines neuronal sensitivity to signaling molecules. Although the removal of activated receptors has been widely studied, their replacement has been a less popular topic. “Historically, most people thought of it as simply a bulk-flow process,” says van Zastrow. “The bias in the field, and one that I held, honestly, is that insertion processes would be unregulated.”
The UCSF group has now, however, identified two distinct types of insertion events—both regulated. In the predominant type, GFP-tagged β2 adrenergic receptors (β2ARs) moved laterally away from the insertion site almost immediately. In the second, the receptors were temporarily stuck at the insertion site for an average of 30 seconds before diffusing away suddenly. Neither resembled axonal “kiss-and-run” exocytic events, in which cargo is deposited but then immediately removed.
The two somatodendritic insertion types were oppositely affected by β2AR activation. Transient insertion events (those that diffuse immediately) were inhibited by a PKA-dependent pathway, whereas persistent insertion events increased. Fewer transient insertions probably dampen overall signaling; the increase in persistent events might favor a different signaling cascade, particularly if they represent clustered receptors.