A cell-permeable phospholipase Cgamma1-binding peptide transduces neurons and impairs long-term spatial memory.
Growth factor-mediated signaling has emerged as an essential component of memory formation. In this study, we used a phospholipase C gamma 1 (PLCgamma1) binding, cell-penetrating peptide to sequester PLCgamma1 away from its target, the phosphotyrosine residues within the activated growth factor receptor. Peptides appear to transduce neurons but not astrocytes or oligodendrocytes. The presence of the peptides in the hippocampus during training in the Morris water maze significantly impaired long-term memory, but not memory acquisition. These results, along with previous studies on extracellular signal-regulated kinase (ERK) and phosphoinositide-3 kinase (PI3K), implicate all three key growth factor receptor-activated intracellular signaling pathways in memory storage.
Blum
Sonja
S
Department of Neurobiology and Anatomy, The Vivian L. Smith Center for Neurologic Research, The University of Texas Medical School, Houston, Texas 77225, USA.
Dash
Pramod K
PK
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000502:physiology; D004193:Discrimination Learning / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D008568:Memory / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism; D009924:Organ Culture Techniques; D051966:Phospholipase C gamma; D010748:Phosphopeptides / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D020318:Rats, Long-Evans; D017978:Receptors, Growth Factor / Q000378:metabolism; D012153:Retention, Psychology / Q000502:physiology*; D015290:Second Messenger Systems / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013028:Space Perception / Q000502:physiology; D014163:Transfer, Psychology / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism*
D002352:Carrier Proteins; D010748:Phosphopeptides; D017978:Receptors, Growth Factor; D010738:Type C Phospholipases; D051966:Phospholipase C gamma