Cdc42 Interacting Protein 4 (CIP4),
Involvement in Endocytosis and
Membrane Protrusion
Genti Gjyzeli
Kelly Mitok
Corey O’Reilly
CIP4 Structure
SH3
SH3
FBAR
HR1
HR1
FBAR: Shimada et al., 2007
SH3: Miyamoto et al., unpublished
HR1: Kobashigawa et al., 2009
CIP4 is involved in Endocytosis
Pitts, 2005
Shimada et al., 2007
FBAR domain
FBAR and HR1 domains
FB
Membrane Interacting Residues in
Endocytosis
Intracellular
Extracellular
Shimada et al., 2007
CIP4 in Endocytosis
Intracellular
Extracellular
FBAR: Shimada et al., 2007
SH3: Miyamoto et al., unpublished
HR1: Kobashigawa et al., 2009
Overexpression of CIP4 in neurons gives large protrusion
Normal Cortical Neuron
Overexpression of CIP4
Microtubule CIP4 Actin
Microtubules Actin
Pictures provided by Dent and Saengsawang
CIP4 Location in Growth Cone
Actin CIP4
Video provided by Dent and Saengsawang
CIP4 Location in Growth Cone
Actin CIP4
Video provided by Dent and Saengsawang
Residues that may be important in
protrusion
Intracellular
Extracellular
Shimada et al., 2007
CIP4 in Protrusion
Intracellular
Extracellular
FBAR: Shimada et al., 2007
SH3: Miyamoto et al., unpublished
HR1: Kobashigawa et al., 2009
Future Mutation Studies to Determine
Important Residues in Protrusion
Shimada et al., 2007
Future Studies to analyze Potential
Phosphoregulation of CIP4
Roberts-Galbraith et al., 2010
Diseases Associated with CIP4
• Huntington’s Disease
• Cancer
Joshi, 2010
Biocore Instructional Materials
• Learning Goals:
– Predict how domains of a protein can influence it’s overall
function
– Electrostatic interactions of protein with membrane
– One protein  one function
– Predict protein function from location in cell
– Endocytosis
• Materials:
– Jmol tutorial
– Cellular landscape
– Animation
Thanks
Michelle Harris
Erik Dent
Witchuda Saengsawang
Tim, Mark, and Margaret at CBM of MSOE
The other UW-Madison team for their feedback