【Date】Feb. 16 (Tue), 2016 12:00～13:00
【Venue】Conference room, 1st floor,
Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University
【Abstract】
The transport of fluids, gases, signaling molecules, and cells within the vertebrate body is mediated by an extensive vascular network consisting of arteries, capillary beds and veins. The proper function of blood vessels contributes to homeostasis of the whole body. Vascular problems contribute to numerous human diseases such as atherosclerosis. The vasculature expands substantially during development with blood flow. Expansion of existing vasculature, termed angiogenesis, must tightly coordinate a complex series of steps as diverse as EC proliferation, sprouting from existing vessels, migration, EC-EC contact formation, tubulogenesis and remodeling. ECs have three different cellular polarities; sprouting ECs have front-rear polarity, and established endothelial tubes have apical-basal polarity and planar cell polarity (PCP) parallel to blood flow. Thus, polarity switching and maintenance are a key feature of this process. Previous works have revealed the molecular basis of endothelial sprouting behavior. We have shown that ephrin-B2 forms a protein complex with Partitioning defective 3 (PAR-3) and atypical PKC (aPKC), controlling VEGFR endocytosis during this process (Wang et al 2010 & Nakayama et al 2013). PAR-3 and aPKC were originally identified as the regulator of asymmetric cell division of C-elegans zygote. Moreover, a growing body of evidence is accumulating to show that these polarity proteins are crucial for controlling cell polarity across many cell types and animal species. However, the role of PAR-3 and aPKC in endothelial polarity during angiogenesis and blood vessel homeostasis remains elusive. Here we clarify the role of PAR-3 and aPKC in endothelial polarity and homeostasis.
【References】
1. Wang Y*, Nakayama M*, Pitulescu ME*, Schmidt TS*, Bochenek ML, Akira Sakakibara A, Adams A, Davy A, Deutsch U, Lüthi U, Barberis A, Benjamin LE, Mäkinen T, Nobes CD, and Adams RH Ephrin–B2 controls VEGF–induced angiogenesis and lymphangiogenesis. (2010)
Nature 465: 483-486 *Equal contribution
2. Nakayama M*, Nakayama A, Van Lessen M, Yamamoto H, Hoffmann S, Drexler HCA, Itoh N, Hirose T, Cooper JA, Ohno S, Kaibuchi K, Adams RH*. Spatial regulation of VEGFR endocytosis in angiogenesis (2013) Nature Cell Biology 15: 249-60 *corresponding author
【Contact】 Dept. of Kidney Development, Ryuichi Nishinakamura (Ext. 6615)
