Striatin-Interacting Protein 1 (STRIP1) stabilizes cytoskeletal organizers to ensure barrier formation and planar cell polarity in the skin epidermis

Summary: Abstract Body: The skin epidermal keratinocytes undergo cellular rearrangements during development to establish barrier function and organize hair follicles. Cell movement is accompanied by junctional remodeling within and across the layers. Although the executioners of cytoskeletal organization are well-established, their upstream cues that underlie proper epidermal and hair development are largely unknown. We have previously shown that Striatin-Interacting Protein 1 (STRIP1), a core component of the Striatin-Interacting Phosphatases and Kinases (STRIPAK) complex that regulates the activity of PP2A, is essential for actin organization to facilitate cellular migration and intercalation during mouse gastrulation. Here, we hypothesize that STRIP1 is required to mediate the STRIPAK functions in cytoskeletal remodeling during epidermal and hair morphogenesis. Functionally, the epidermal loss of STRIP1 results in a thinner epidermis with less hair follicles and lethality of about half of the mutants due to barrier defects. The granular keratinocytes possess wavy cell borders and reduced mechanical tension in Strip1 mutant epidermis, suggesting perturbed actin-myosin interaction. Interestingly, Strip1 deficiency results in the loss of CTTNBP2NL, and actin organizer and associated member of the STRIPAK, at the protein level both in vivo and in vitro. Moreover, hair follicles in Strip1 mutant epidermis are misoriented indicating defective planar cell polarity in the absence of STRIP1. Strikingly, DVL2 is destabilized and VANGL2 mislocalized in Strip1 mutant epidermis. Collectively, our data show that STRIP1 regulates cytoskeletal organization to ensure intact barrier formation and planar cell polarity in the epidermis. Lisa Wirtz^{1, 2, 3}, Houda Khatif¹, Ekaterina Soroka¹, Charlotte Meyer-Gerards¹, Tyler Hoard², Hisham Bazzi^{1, 2, 3} 1. Department of Cell Biology of the Skin, CECAD, Universitat zu Koln, Cologne, NRW, Germany. 2. Department of Cell & Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, United States. 3. Skin Research Center, University of Michigan Medical School, Ann Arbor, MI, United States. Epidermal Structure and Barrier Function