BIPN 148Lecture 10

Biochemical Basis of LTP

Modulation of NMDA receptors

Calcium signaling and LTP/LTD

Calcium activation of CaM kinases

T TT

Catalytic Autoinhibitory Self-association

InhibitoryCalmodulin

Binding

286Autonomous

Activity

305/306Inhibitory

A

B C

P P

Structure of CaMKII

Verdaguer et al. (1999) Embo. J. 18:6329-6338.

Calcium activation of CaMKII

Calcium activation of CaMKII

Persistent activation of CaMKII

Temporal Integration of a Ca Signal by CaMKII

Dineley et al. (2001) J. Neurochem. 77:961-971.

NMDAReceptor

CaMKII

Transient CaMKIIActivation

Thr 286Autophosphorylation(persistently active)

NMDAR Association(persistently active)

CaMKII

CaMKII

Ca++/CaM

Effects of Ca/CaM on CaMKII

LTP in Thr286A mutant mice

LTP in Thr286A mutant mice