Johanna Ivaska: Finding opposing forces in integrins

JCB • VOLUME 208 • NUMBER 6 • 2015 652 Johanna Ivaska will tell you that she never planned to continue studying integrins, the sticky transmembrane receptors that grab onto a cell’s extracellular environment, after her PhD. But somehow the integrins seemed to be stuck on her. As a PhD student at the University of Turku in Finland, Ivaska chose a laboratory investigating collagen-binding integrins as a way to move into cancer research. When choosing a postdoctoral lab, Ivaska wanted to gain some experience in intracellular signaling, so she joined Peter Parker’s group at Cancer Research UK in London working on the protein kinase C (PKC) pathway. She took the lead on an open project to investigate how integrins and PKCs work together in cancer migration—and integrins have become integral to her own line of inquiry ever since. In 2003, she moved back to Turku and set up her own group at VTT Technical Research Centre of Finland. In yeast two-hybrid studies using the cytoplasmic tail domains of integrin subunits as bait, her lab pulled out two surprising “fi sh.” The fi rst was a phosphatase, which her group demonstrated was activated by adhesion and decreased EGF receptor phosphorylation (1). The second subunit binder was a Rab GTPase that regulated the traffi cking of integrins through endocytic vesicles (2). In 2011, her group identifi ed the fi rst ubiquitously expressed 1-integrin inactivator, SHARPIN (3, 4), another subunit binding partner. Most recently, her laboratory, now based at the University of Turku, has investigated the unconventional myosin-X, a transporter of integrins, and its role in breast cancer metastasis (5). This month, Ivaska shared with JCB why she can’t seem to escape discoveries about the lesser-studied integrin subunit and her penchant for outdoor adventures. GRABBY MOLECULES How do you describe integrins—some of the most sophisticated of receptor molecules—to students? I always describe them as the hands of the cell. Or the hands and feet, I suppose. They’re the things that a cell uses to grab its environment and hold on or pull itself forward. Integrins are either holding onto other cells or a matrix protein in the environment. But that’s only one half of what integrins do, because they then transmit signals from what they’re holding onto inside the cell. One of the most important, unique properties of integrins is that they act as mechanosensors that can signal in both directions. They act like springs and tell the cell about environmental stiffness and composition. That’s called outside-in signaling. On the other hand, intracellular events can tell the cell to activate integrins. This inside-out signaling tells the cell to grasp harder or migrate faster.