Neuronal fodrin proteolysis occurs independently of excitatory amino acid-induced neurotoxicity

Neuron. 1991 Mar;6(3):445-54. doi: 10.1016/0896-6273(91)90252-u.

Abstract

In cultured cerebellar granule cells, the total amount of fodrin alpha subunit increased 3-fold between 0 and 10 days in vitro and fodrin mRNA increased 5-fold. The exposure of cerebellar neurons to NMDA induced the accumulation of a 150 kd proteolytic fragment of fodrin. The NMDA-induced breakdown of fodrin was time-, concentration-, and Ca2(+)-dependent and was inhibited by APV, Mg2+, or the calpain I inhibitor N-acetyl-Leu-Leu-norleucinal. Kainate caused fodrin proteolysis through indirect activation of NMDA receptors. Quisqualate was ineffective. The NMDA-induced degradation of fodrin occurred under conditions that did not cause degeneration of cultured cerebellar neurons. These results show that Ca2+/calpain I-dependent proteolysis of fodrin is selectively associated with NMDA receptor activation; however, fodrin proteolysis per se does not play a causal role in NMDA-induced toxicity in cerebellar granule cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Northern
  • Calcium / pharmacology
  • Calcium Channels / drug effects
  • Calcium Channels / physiology
  • Calpain / pharmacology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cattle
  • Cells, Cultured
  • Cerebellum / cytology
  • Cerebellum / drug effects
  • Cerebellum / metabolism
  • Dose-Response Relationship, Drug
  • Fluorescent Antibody Technique
  • Kainic Acid / pharmacology
  • Leupeptins / pharmacology
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • N-Methylaspartate / toxicity*
  • Neurons / drug effects
  • Neurons / metabolism*
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Glutamate
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Receptors, Neurotransmitter / drug effects
  • Receptors, Neurotransmitter / physiology
  • Time Factors

Substances

  • Calcium Channels
  • Carrier Proteins
  • Leupeptins
  • Microfilament Proteins
  • RNA, Messenger
  • Receptors, Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter
  • fodrin
  • acetylleucyl-leucyl-norleucinal
  • N-Methylaspartate
  • Calpain
  • Kainic Acid
  • Calcium