Synaptopodin Regulates Plasticity of Dendritic Spines in Hippocampal Neurons

Abstract

The spine apparatus is an essential component of dendritic spines of cortical and hippocampal neurons, yet its functions are still enigmatic. Synaptopodin (SP), an actin-binding protein, is tightly associated with the spine apparatus and it may play a role in synaptic plasticity, but it has not yet been linked mechanistically to synaptic functions. We studied endogenous and transfected SP in dendritic spines of cultured hippocampal neurons and found that spines containing SP generate larger responses to flash photolysis of caged glutamate than SP-negative ones. An NMDA-receptor-mediated chemical long-term potentiation caused the accumulation of GFP-GluR1 in spine heads of control but not of shRNA-transfected, SP-deficient neurons. SP is linked to calcium stores, because their pharmacological blockade eliminated SP-related enhancement of glutamate responses, and release of calcium from stores produced an SP-dependent increase of GluR1 in spines. Thus, SP plays a crucial role in the calcium store-associated ability of neurons to undergo long-term plasticity.

Cumulus cell gene expression following the LH surge in bovine preovulatory follicles: potential early markers of oocyte competence

“…Following the LH surge, we showed up the overexpression of several neuronal-related genes such as THBS1 (Liauw et al 2008), FGF2 (Chen et al 2010), MYO1D (Brown & Bridgman 2004), SYNPO (Vlachos et al 2009), and CD9 (Ishibashi et al 2004;Figs 2 and 4). Strikingly, the common functions ensured by these genes were mainly neuron plasticity, neurogenesis (including the dendrogenesis and the axogenesis), and synaptogenesis.…”

Location matters: the endoplasmic reticulum and protein trafficking in dendrites

“…Likewise, a dominant negative KIF5 alters the intracellular localization of ER retained wild-type GABA B R1 but not of a subunit with mutations in the ER retention motif (Vidal et al, 2007). The role of molecular motors in ER transport along dendrites is further supported by evidence indicating that resident proteins of the ER move from the soma to dendrites in a microtubule and kinesin-dependent manner (Bannai et al, 2004;Copray et al, 1996;Vlachos et al, 2009). Whether the mobile compartment is a vesicular ER component or a more complex dynamic structure, such as large protein complexes moving through dilated or bulged tubular ER membranes, remains to be determined.…”

“…The SER volume represents a small fraction of a dendrite (3,2 % of dendrite volume) and does not change with age, despite the fact that its surface increases 1,7 fold from postnatal day 15 to adult in mice (Cooney et al, 2002). The SER is also present in the head or neck of 20% of adult dendritic spines, where it occasionally associates to a prominent specialization called the spine apparatus (SA) that can be identifi ed by labeling the actin-binding protein synaptopodin (Cooney et al, 2002;Vlachos et al, 2009).…”

“…For example, in spite of its continuous structure, the ER has a heterogeneous distribution of inositol 1,4,5-trisphosphate receptors, ryanodine receptors and calreticulin (Bannai et al, 2004;Copray et al, 1996;Vlachos et al, 2009). The differential localization of proteins related to Ca 2+ signaling is an important factor for the spatial regulation of Ca 2+ release, allowing the control of Ca 2+ transport in local domains (Petersen and Verkhratsky, 2007).…”

“…Recently, a more complex scenario of secretory organelles has supported an alternative model (Pierce et al, 2001;Vlachos et al, 2009). The model rests on the existence of a local secretory route in which the functional ER is distributed throughout the neuron and releases cargo from dERES towards Golgi outposts, including local sorting stations in the generation and maintenance of neuronal microdomains (Horton and Ehlers, 2003) (Figure 2).…”