Postsynaptic density protein

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PSD-95PSD-95

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You may include any references to papers as in: the use of JSmol in Proteopedia [1] or to the article describing Jmol [2] to the rescue.

Function

PSD-95 is a scaffolding protein that is found in the postsynaptic density (PSD) in the excitatory neurons of the cerebral cortex. This protein belongs to the Membrane-associated guanylate kinases (MAGUK) family. The proteins of the MAGUK family have been found to be a key factor in many processes. These processes include the development of tissues, communications between cells, cellular charge activation, and signal transduction between cells just to name a few (Zhu et al., 2011). PSD-95 permeates the PSD, a large curved protein complex that lines the postsynaptic membrane (PSM) or the cellular interior of a synapse. This protein complex’s primary function is one of support. It is known to hold not only synaptic receptors in place in the membrane but it holds their respective signaling molecules as well. PSD-95 is integral to the organization of these receptors, as well as the downstream signaling proteins. Due to the scaffolding directive of PSD-95, its structure is actually a series of proteins to make a much larger binding protein complex. PSD-95 not only enriches synaptic transmissions but it is also known to play a major role in synaptic plasticity through the lattice it makes at the synaptic membrane.

With PSD-95 being so close to the cell membrane, it can be identified and labeled by antibodies from both sides of the plasma membrane. Due to its location it is able to interact with membrane bound proteins including ion channels, adhesion molecules, and various receptors. The most important of these interactions is considered to be its ability to sort signaling complexes in the plasma membrane.

Disease

There are more than 130 diseases are attributed to changes in the proteome of excitatory synapses. Given that PSD-95 belongs to the proteome of excitatory synapses, research has found that any mutations with PSD-95 caused complications not only for how quickly synapses transmitted neurotransmitters but its capability to conform to new stresses. Therefore, since PSD-95 is integral for synaptic stability, a decrease in PSD-95 has substantial neurological effects based on age and the area of the brain affected.

1. Media Prefrontal Cortex - Under normal circumstances, PSD-95 continues to increase from birth until peaking during adolescents. However, if the PSD-95 is decreased, it will affect the medial prefrontal cortex (mPFC) which is responsible for cognition, working memory, and sociability (Coley, 2019). Researchers found that the PSD-95 knockout mice lacked sociability and exhibited both learning and working memory deficiencies. The dysfunction of PSD-95 is believed to manifest to some degree in humans as either schizophrenia or as autism (Coley, 2019). It has also been linked to Alzheimer’s by a research study. 2. Superior Temporal Sulcus - This research study focused on the superior temporal sulcus. The disease is mainly characterized by neuronal damage, neuronal death, and brain atrophy. The study found that in a group of post-mortem subjects; demented subjects had 50% less PSD-95 concentration than the control group (Perez-Nievas, 2013). This was compared to a group that had many of the same morphological signs as those with Alzheimer’s but suffered no adverse effects from it. This group had significantly more PSD-95 than a normal brain, perhaps to counter act the degrading aspects. 3. Corpus Striatum – A study of cocaine abuse using a mice study suggests that psychostimulants decrease the PSD-95 levels in both the dorsal and ventral portions of the striatum though the hippocampus and cortex were unaffected. While less than 2 injections made little change in PSD-95 levels, 3 to 10 injections resulted in substantial chronic PSD-95 loss; however, 11 or more injections showed no additional decreases (Yao et al., 2004). When studied months after the last injection, the deficits in PSD-95 remained, suggesting long-term neuronal effects of drug use.

Relevance

Structural highlights

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ReferencesReferences

  1. Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
  2. Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Blair Matzker, Michal Harel, Jaime Prilusky