title: SH2B1 increases the numbers of IRSp53-induced filopodia.
abstract: BACKGROUND
  Filopodia are actin-rich membrane protrusions that play instrumental roles in development, cell migration, pathogen detection, and wound healing. During neurogenesis, filopodium formation precedes the formation of dendrites and spines. The insulin receptor substrate protein of 53kDa (IRSp53) has been implicated in regulating the formation of filopodia. Our previous results suggest that a signaling adaptor protein SH2B1β is required for neurite outgrowth of hippocampal neurons and neurite initiation of PC12 cells. Thus, we hypothesize that IRSp53 and SH2B1β may act together to regulate filopodium formation.
  
  
  METHODS
  To determine the contribution of IRSp53 and SH2B1β in the formation of filopodia, we transiently transfect IRSp53 and/or SH2B1β to 293T cells. Cell morphology and protein distribution are assessed via confocal microscopy and subcellular fractionation. Total numbers of filopodia and filopodium numbers per perimeter are calculated to show the relative contribution of IRSp53 and SH2B1β.
  
  
  RESULTS
  In this study, we show that SH2B1β interacts with IRSp53 and increases the number of IRSp53-induced filopodia. One mechanism for this enhancement is that IRSp53 recruits SH2B1β to the plasma membrane to actively promote membrane protrusion. The increased numbers of filopodia likely result from SH2B1-mediated cytoplasmic extension and thus increased cell perimeter as well as IRSp53-mediated filopodium formation.
  
  
  CONCLUSIONS
  Taken together, this study provides a novel finding that SH2B1β interacts with IRSp53-containing complexes to increase the number of filopodia.
  
  
  CONCLUSIONS
  A better understanding of how SH2B1β and IRSp53 promote filopodium formation may have clinical implication in neurogenesis and regeneration.
authors.affiliation: Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 30013, Taiwan, ROC.
authors.forename: Shao-Jing
authors.initials: SJ
authors.lastname: Hong
authors.affiliation: Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 30013, Taiwan, ROC.
authors.forename: Szu-Ting
authors.initials: ST
authors.lastname: Liu
authors.affiliation: Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 30013, Taiwan, ROC.
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 30013, Taiwan, ROC; Department of Medical Science, National Tsing Hua University, Hsinchu 30013, Taiwan, ROC. Electronic address: lchen@life.nthu.edu.tw.
authors.forename: Linyi
authors.initials: L
authors.lastname: Chen
keywords: Filopodia; IRSp53; Membrane protrusion; SH2B1