Cdc42 Interacting Protein 4 (CIP4), Involvement in Endocytosis and Membrane Protrusion

Cdc42 Interacting Protein 4 (CIP4), Involvement in Endocytosis and

Membrane ProtrusionGenti GjyzeliKelly Mitok

Corey O’Reilly

CIP4 Structure

FBARHR1

SH3 SH3

HR1

FBAR: Shimada et al., 2007SH3: Miyamoto et al., unpublishedHR1: Kobashigawa et al., 2009

CIP4 is involved in Endocytosis

FB

FBAR domain

FBAR and HR1 domains

Shimada et al., 2007

Pitts, 2005

Membrane Interacting Residues in Endocytosis

Extracellular

Intracellular

Shimada et al., 2007

CIP4 in Endocytosis

Extracellular

Intracellular

FBAR: Shimada et al., 2007SH3: Miyamoto et al., unpublishedHR1: Kobashigawa et al., 2009

Overexpression of CIP4

Microtubules ActinMicrotubule

Overexpression of CIP4 in neurons gives large protrusion

Normal Cortical Neuron

ActinCIP4

Pictures provided by Dent and Saengsawang

CIP4 Location in Growth Cone

CIP4ActinVideo provided by Dent and Saengsawang

CIP4 Location in Growth Cone

CIP4ActinVideo provided by Dent and Saengsawang

Residues that may be important in protrusion

Extracellular

Intracellular

Shimada et al., 2007

CIP4 in Protrusion

Extracellular

Intracellular

FBAR: Shimada et al., 2007SH3: Miyamoto et al., unpublishedHR1: 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 HarrisErik DentWitchuda SaengsawangTim, Mark, and Margaret at CBM of MSOEThe other UW-Madison team for their feedback