ZFIN ID: ZDB-PUB-100719-41
KBP interacts with SCG10, linking Goldberg-Shprintzen syndrome to microtubule dynamics and neuronal differentiation
Alves, M.M., Burzynski, G., Delalande, J.M., Osinga, J., van der Goot, A., Dolga, A.M., de Graaff, E., Brooks, A.S., Metzger, M., Eisel, U.L., Shepherd, I., Eggen, B.J., and Hofstra, R.M.
Date: 2010
Source: Human molecular genetics   19(18): 3642-3651 (Journal)
Registered Authors: Shepherd, Iain T.
Keywords: none
MeSH Terms:
  • Animals
  • Carrier Proteins/genetics
  • Carrier Proteins/metabolism*
  • Cell Line
  • Cells, Cultured
  • Craniofacial Abnormalities/genetics
  • Craniofacial Abnormalities/metabolism
  • Disease Models, Animal
  • HeLa Cells
  • Hirschsprung Disease/genetics
  • Hirschsprung Disease/metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins/genetics
  • Intracellular Signaling Peptides and Proteins/metabolism*
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Microtubules/metabolism*
  • NIH 3T3 Cells
  • Neurogenesis*
  • Neurons/cytology
  • Neurons/metabolism
  • PC12 Cells
  • Protein Binding
  • Rats
  • Serpins/genetics
  • Serpins/metabolism*
  • Stathmin/genetics
  • Stathmin/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 20621975 Full text @ Hum. Mol. Genet.
Goldberg-Shprintzen syndrome is a rare clinical disorder characterized by central and enteric nervous system defects. This syndrome is caused by inactivating mutations in the Kinesin Binding Protein (KBP) gene, which encodes a protein of which the precise function is largely unclear. We show that KBP expression is up-regulated during neuronal development in mouse cortical neurons. Moreover, KBP-depleted PC12 cells were defective in NGF-induced differentiation and neurite outgrowth, suggesting KBP is required for cell differentiation and neurite development. To identify KBP interacting proteins, we performed a yeast two-hybrid screen and found that KBP binds almost exclusively to microtubule-associated or related proteins, specifically SCG10 and several kinesins. We confirmed these results by validating KBP interaction with one of these proteins: SCG10, a microtubule destabilizing protein. Zebrafish studies further demonstrated an epistatic interaction between KBP and SCG10 in vivo. To investigate the possibility of direct interaction between KBP and microtubules, we undertook co-localization and in vitro binding assays, but found no evidence of direct binding. Thus, our data indicates that KBP is involved in neuronal differentiation and that the central and enteric nervous system defects seen in Goldberg-Shprintzen syndrome are likely caused by microtubule-related defects.