On Monday afternoon at ASCB 2013, I took in the minisymposium on the Spatial Regulation of Signaling, organized by Johanna Ivaska (University of Turku) and Rajat Rohatgi (Stanford). The session covered a lot of ground, exploring many different signaling events taking place in many different parts of the cell.
Several of the talks discussed pathways involved in cell adhesion. Jonna Alanko (from Ivaska’s lab) described an interesting new way of compartmentalizing the signals from integrin adhesion molecules. Brian Beaty (from John Condeelis’ lab at the Albert Einstein College of Medicine) discussed the role of integrin signaling in the formation of invadopodia, the actin-rich membrane protrusions that drive cancer cell invasion through the extracellular matrix. Beaty, who has previously shown that β1 integrin localizes to invadopodia, described how integrin-binding proteins stimulate actin polymerization in invadopodia. And Matthew Kutys (a member of Ken Yamada’s laboratory at the NIH) discussed how cells migrating through different types of extracellular matrix activate different Rho GTPase pathways that affect their mode of motility.
Cecile Gauthier-Rouviere (Montpelier) focused on intercellular adhesions, revealing that flotillins 1 and 2 promote the assembly of adherens junctions by stabilizing the presence of cadherin adhesion molecules in plasma membrane microdomains at cell-cell contacts.
Sigrid Nachtergaele (from Rohatgi’s group) described how the oxysterol 20(S)-OHC activates the Hedgehog signaling pathway by binding to the seven-pass transmembrane protein Smoothened. Activated smoothened accumulates in the primary cilium, and this organelle – often described as the cell’s antenna – is a critical location for many other signaling pathways in addition to the Hedgehog pathway. Mutations that disrupt ciliary function cause a group of human diseases – ciliopathies – characterized by a diverse set of symptoms reflecting the variety of tissues and signaling pathways that can be affected. Obesity is a common feature of ciliopathies and Alexander Loktev (working with Peter Jackson at Genentech and at Stanford) described how the BBSome – a group of proteins mutated in the ciliopathy Bardet-Biedl Syndrome – transports the G protein-coupled receptor NPY2R into the cilia of neurons in the hypothalamus. NPY2R and its ligand PYY2-36 suppress the appetite, but mice lacking BBSome components couldn’t localize NPY2R to the primary cilium and couldn’t activate the pathway, leading to increased food intake.
And finally, Art Alberts (from the Van Andel Research Institute in Grand Rapids) discussed the various ways that cells can exchange membrane with one another. Different cell types carry out this exchange in different ways, but it appears to be an almost universal process that allows cells to exchange material and influence each other’s behavior.