The spine apparatus (SA) is a specialized form of endoplasmic reticulum (ER) that is found in a subpopulation of dendritic spines in central neurons. It was discovered by Edward George Gray in 1959 when he applied electron microscopy to fixed cortical tissue. The SA consists of a series of stacked discs that are connected to each other and to the dendritic system of ER-tubules. The actin binding protein synaptopodin (which was originally described in podocytes of the kidney) is an essential component of the SA. Mice that lack the gene for synaptopodin do not form a spine apparatus. The SA is believed to play a role in synaptic plasticity, learning and memory, but the exact function of the spine apparatus is still enigmatic.
Morphology The spine apparatus consists of membranous saccules (discs) and tubules surrounded by wispy filamentous material and is mainly found in large mushroom-shaped dendritic spines. The wispy filamentous material is the cytoskeletal network, mainly f-actin, which is responsible for the maintenance and alteration of spine shape. The spine apparatus is connected to the smooth-surfaced endoplasmic reticulum of the dendrite. Consisting of continuous parallel flattened cisternae, the spine apparatus has a large surface area which is important for its function. The spine apparatus occupies a large portion of the volume of the spine stalk, which may increase the longitudinal resistance between spine and dendrite Therefore, the spine apparatus could have a direct effect on the membrane potential of the spine plasma membrane when the synapse is active. The connection to the smooth endoplasmic reticulum suggests a potential pathway for the transfer of proteins and lipids between the spine and dendrite. The spine apparatus could also function as a reservoir for calcium ions.
Function
Local protein synthesis and trafficking For some time, the function of the spine apparatus has been considered enigmatic. Recent evidence, however, suggests the spine apparatus may possess several distinct functions. After elucidating the structure of the spine apparatus, Spacek and Harris noted a continuation of the smooth endoplasmic reticulum into the spine apparatus, where it then takes on a lamellar structure. This observation suggests the SA might play a role in vesicular transport, although a specific mechanism is not yet clear. Furthermore, Pierce et al. proposed that the spine apparatus may be involved in post-translational protein processing, similar to that observed in the Golgi apparatus, and function in the post-translational processing of GluR1 and GluR2 subunits, which are locally translated in dentritic spines, of AMPA receptors. The spine apparatus has also been shown to be involved in the post-translational processing and spatial delivery of NMDA receptors, which also function as glutamate receptors and play a significant role in controlling synaptic plasticity. The appearance of molecular markers for satellite secretory pathways provides further evidence that the spine apparatus plays a role in local integral membrane protein translocation and processing. More specifically, the protein translocation site marker (Sec61α) and the Golgi cisternae markers (giantin and α-mannosidase II) have been observed in the spine apparatus.
Calcium signaling
Synaptic activity triggers Ca2+ influx into dendritic spines via NMDA receptors and voltage-dependent calcium channels. Free Ca2+ ions are rapidly removed from the cytoplasm through Na+/Ca2+ exchangers in the plasma membrane and by sarco/endoplasmic reticulum Ca2+ ATPases (SERCA pumps) that mediate Ca2+ uptake into the smooth endoplasmic reticulum (sER). The spine apparatus, as a sub-compartment of the sER, has a large surface area and is thought to act as an efficient calcium buffer inside the spine (Figure 2). Recent studies have shown that the spine apparatus is also able to release Ca2+ through inositol trisphosphate receptors (IP3Rs) or ryanodine receptors (RyRs). The calcium-sensitive nature of IP3Rs and RyRs makes both receptors capable of regenerative calcium-induced calcium release (CICR). In dendritic shafts and spines of hippocampal neurons the presence of both RyRs and IP3Rs has been shown by immunostaining. Ca2+ release is triggered by glutamate release, activating Group I metabotropic glutamate receptors (mGluRs). The downstream signaling cascade leads to elevated IP3 levels inside the spine (Figure 2) which trigger Ca2+ release events only in those spines that contain sER. Specifically, CICR activates RyR mostly located at the base of dendritic spines, while SERCA pumps are located in the spine head. This asymmetry organization of RyR versus SERCA leads to fast calcium signaling at the base of the dendritic spine, leading to SA calcium depletion. Calcium is finally refilled by ORAI-STIM1 mostly located in clusters in the spine head. The slow calcium influx through this store operated Calcium Entry (SOCE) prevents activation of the RyR triggered by fast synaptic inputs.
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