Deceivingly dynamic: Learning-dependent changes in stathmin and microtubules

Abstract

Microtubules, one of the major cytoskeletal structures, were previously considered stable and only indirectly involved in synaptic structure and function in mature neurons. However, recent evidence demonstrates that microtubules are dynamic and have an important role in synaptic structure, synaptic plasticity, and memory. In particular, learning induces changes in microtubule turnover and stability, and pharmacological manipulation of microtubule dynamics alters synaptic plasticity and long-term memory. These learning-induced changes in microtubules are controlled by the phosphoprotein stathmin, whose only known cellular activity is to negatively regulate microtubule formation. During the first eight hours following learning, changes in the phosphorylation of stathmin go through two phases causing biphasic shifts in microtubules stability/instability. These shifts, in turn, regulate memory formation by controlling in the second phase synaptic transport of the GluA2 subunit of AMPA receptors. Improper regulation of stathmin and microtubule dynamics has been observed in aged animals and in patients with Alzheimer’s disease and depression. Thus, recent work on stathmin and microtubules has identified new molecular players in the early stages of memory encoding.

Eosinophil cytolysis on Immunoglobulin G is associated with microtubule formation and suppression of rho‐associated protein kinase signalling

“…Taken together, these observations indicate that the presence of MT arrays per se is not sufficient to induce cytolysis and suggest a role for MT dynamics in cytolysis. MT dynamics are usually defined by rates of microtubule growth and shortening, and the frequencies of catastrophes and rescues . To demonstrate changes in events linked to MT growth and rescue frequency, we analysed the phosphorylation status of two regulators of MT polymerization/depolymerization and catastrophe/rescue events, stathmin and MAP4 .…”

CRTC1 Nuclear Translocation Following Learning Modulates Memory Strength via Exchange of Chromatin Remodeling Complexes on the Fgf1 Gene

“…Deficits in microtubule-mediated intracellular transport impair synaptic plasticity and memory formation (Shumyatsky et al, 2005; Uchida et al, 2014; Uchida and Shumyatsky, 2015), suggesting that nuclear translocation of CRTC1 may be dependent on microtubules. Injection of nocodazole, a microtubule destabilizer, into the hippocampus 1 h before 3-shock CFC blocked the increase in nuclear CRTC1 and the decrease in synaptic CRTC1 but did not change whole-cell CRTC1 levels, as measured 1 h following CFC (Figure S5H).…”

Of microtubules and memory: implications for microtubule dynamics in dendrites and spines

“…Certain proteins within cells—most notably tubulin, actin, intermediate filaments, and septins—have the ability to form polymeric structures that give rise to what is termed the cytoskeleton. Although the name suggests a rather stable network of filaments, the cytoskeleton is anything but (Uchida and Shumyatsky, 2015). The cytoskeleton is in constant motion through subunit exchange, assembling and disassembling via intrinsic mechanisms inherent in each type of polymer and regulated by myriad polymer-associated proteins.…”