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Role of Cdc42 in neurite outgrowth of PC12 cells and cerebellar granule neurons

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Abstract

Inactivation of Rho GTPases inhibited the neurite outgrowth of PC12 cells. The role of Cdc42 in neurite outgrowth was then studied by selective inhibition of Cdc42 signals. Overexpression of ACK42, Cdc42 binding domain of ACK-1, inhibited NGF-induced neurite outgrowth in PC12 cells. ACK42 also inhibited the neurite outgrowth of PC12 cells induced by constitutively activated mutant of Cdc42, but not Rac. These results suggest that Cdc42 plays an important role in mediating NGF-induced neurite outgrowth of PC12 cells. Inhibition of neurite outgrowth was also demonstrated using a cell permeable chimeric protein, penetratin-ACK42. A dominant negative mutant of Rac, RacN17 inhibited Cdc42-induced neurite outgrowth of PC12 cells suggesting that Rac acts downstream of Cdc42. Further studies, using primary-cultures of rat cerebellar granule neurons, showed that Cdc42 is also involved in the neurite outgrowth of cerebellar granule neurons. Both penetratin-ACK42 and Clostridium difficile toxin B, which inactivates all members of Rho GTPases strongly inhibited the neurite outgrowth of cerebellar granule neurons. These results show that Cdc42 plays a similar and essential role in the development of neurite outgrowth of PC12 cells and cerebellar granule neurons. These results provide evidence that Cdc42 produces signals that are essential for the neurite outgrowth of PC12 cells and cerebellar granule neurons.

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Abbreviations

ACK42:

Cdc42 binding fragment of ACK-1

GAP:

GTPase activating protein

RHG:

Rho GAP domain of p190-A

NGF:

nerve growth factor

NOG:

neurite outgrowth

FCS:

fetal calf serum

GST:

glutathione S-transferase

PLL:

poly-L-lysine

IPTG:

isopropyl-beta-thiogalactopyranoside

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Authors and Affiliations

  1. Department of Pharmacology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 675 Hoes Lane, Piscataway, New Jersey, USA

    Ijaz Ahmed, Yolanda Calle & Alam Nur-E-Kamal

  2. Mitsubishi Kasei Institute of Life Sciences, Machida-shi, Tokyo, 194, Japan

    Shintaro Iwashita

  3. Department of Pharmacology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 675 Hoes Lane, Piscataway, NJ, 08854, USA

    Alam Nur-E-Kamal

Authors
  1. Ijaz Ahmed
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  2. Yolanda Calle
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  3. Shintaro Iwashita
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  4. Alam Nur-E-Kamal
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Correspondence to Alam Nur-E-Kamal.

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These authors contributed equally

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Ahmed, I., Calle, Y., Iwashita, S. et al. Role of Cdc42 in neurite outgrowth of PC12 cells and cerebellar granule neurons. Mol Cell Biochem 281, 17–25 (2006). https://doi.org/10.1007/s11010-006-0165-9

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  • DOI: https://doi.org/10.1007/s11010-006-0165-9

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