The interaction of mPar3 with the ubiquitin ligase Smurf2 is required for the establishment of neuronal polarity.
The Par polarity complex consisting of the evolutionarily conserved proteins mPar3, mPar6, and aPKC regulates cell polarity in many cell types including neurons. Here we show that mPar3 is required for the establishment of neuronal polarity and links the Smurf2 to Kinesin-2. The HECT domain E3 ubiquitin ligase Smurf2 ensures that neurons extend only a single axon by initiating the degradation of inactive Rap1B through the ubiquitin/proteasome system. Its interaction with mPar3 is required to localize Smurf2 to growth cones and restrict Rap1B to the axon. Interfering with the binding of mPar3 to Kinesin-2 or Smurf2 to mPar3 and knockdown of mPar3 by RNAi disrupt the establishment of neuronal polarity through the failure to restrict Rap1B to a single neurite.
Schwamborn
Jens C
JC
Abteilung Molekularbiologie, Institut für Allgemeine Zoologie und Genetik, Westfälische Wilhelms-Universität Münster, Schlossplatz 5, D-48149 Münster, Germany.
Khazaei
Mohammad R
MR
Püschel
Andreas W
AW
D000818:Animals; D019521:Body Patterning; D002352:Carrier Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D008954:Models, Biological; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D051381:Rats; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis* / Q000737:chemistry / Q000502:physiology*; D020668:rap GTP-Binding Proteins / Q000378:metabolism
D002352:Carrier Proteins; C490201:Kif3a protein, rat; D009419:Nerve Tissue Proteins; C472451:Pard3 protein, rat; C526200:Smurf2 protein, rat; D044767:Ubiquitin-Protein Ligases; C492135:Rap1b protein, rat; D016547:Kinesins; D020668:rap GTP-Binding Proteins