SHANK1 is differentially expressed during development in CA1 hippocampal neurons and astrocytes

Abstract

Recent studies have strongly suggested a role for the synaptic scaffolding protein SHANK1 in normal synaptic structure and signaling. Global SHANK1 knockout (SHANK1-/-) mice demonstrate reduced dendritic spine density, an immature dendritic spine phenotype and impairments in various cognitive tasks. SHANK1 overexpression is associated with increased dendritic spine size and impairments in fear conditioning. These studies suggest proper regulation of SHANK1 is crucial for appropriate synaptic structure and cognition. However, little is known regarding SHANK1's developmental expression in brain regions critical for learning. The current study quantified cell specific developmental expression of SHANK1 in the hippocampus, a brain region critically involved in various learning paradigms shown to be disrupted by SHANK1 dysregulation. Consistent with prior studies, SHANK1 was found to be strongly co-expressed with dendritic markers, with significant increased co-expression at postnatal day (P) 15, an age associated with increased synaptogenesis in the hippocampus. Interestingly, SHANK1 was also found to be expressed in astrocytes and microglia. To our knowledge, this is the first demonstration of glial SHANK1 localization; therefore, these findings were further examined via a glial purified primary cell culture fraction using magnetic cell sorting. This additional analysis further demonstrated that SHANK1 was expressed in glial cells, supporting our immunofluorescence co-expression findings. Developmentally, astroglial SHANK1 co-expression was found to be significantly elevated at P5 with a reduction into adulthood, while SHANK1 microglial co-expression did not significantly change across development. These data collectively implicate a more global role for SHANK1 in mediating normal cellular signaling in the brain. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 363-373, 2018.

The role of selected postsynaptic scaffolding proteins at glutamatergic synapses in autism-related animal models

“…SHANK2 and SHANK3 are therefore considered critical for several aspects of neuroplasticity during development [31]. Studies have demonstrated that SHANK1 protein levels increase from birth through early development, followed by a slight decrease in adulthood in the cerebellum and cortex [32]. In fact, SHANK1-3 protein components represent critical determinants of excitatory synaptic function.…”

SHANK1 facilitates non-small cell lung cancer processes through modulating the ubiquitination of Klotho by interacting with MDM2

“…SHANK proteins are mainly localized in the postsynaptic densities (PSD) domain of neuronal excitatory synapses in the central nervous system. At present, it is believed that the SHANK family is essential for the normal function of the nervous system [ 2 – 4 ]. An association between cases of autism spectrum disorder (ASD) and mutations in the genes SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2 and SHANK3 was reported in several large-scale genomic studies.…”