CASK, APBA1, and STXBP1 collaborate during insulin secretion

Zhang, Kai; Wang, Tianyuan; Liu, Xingjing; Yuan, Qingzhao; Xiao, Tin; Yuan, Xiangjiang; Zhang, Yijian; Li, Yuan; Wang, Yao

doi:10.1016/j.mce.2020.111076

Cited by 8 publications

(6 citation statements)

References 32 publications

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“…These findings implied that Munc18-1 is essential for the secretion of DCV, which is often required for the release of neurotrophic factors and axon guidance molecules [43]. This is supported by findings outside the brain, where it was found that Munc18-1 plays a role in facilitating the release of insulin via DCV [49].…”

Section: Stxbp1 Physiologic Functionsupporting

confidence: 60%

STXBP1-Related Disorders: Clinical Presentation, Molecular Function, Treatment, and Future Directions

Freibauer,

Wohlleben,

Boelman

2023

Genes

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In recent years, the affordability and availability of genetic testing have led to its increased use in clinical care. The increased frequency of testing has led to STXBP1 variants being identified as one of the more common variants associated with neurological disorders. In this review, we aim to summarize the common clinical phenotypes associated with STXBP1 pathogenic variants, provide an overview of their known natural history, and discuss current research into the genotype to phenotype correlation. We will also provide an overview of the suspected normal function of the STXBP1-encoded Munc18-1 protein, animal models, and experimental techniques that have been developed to study its function and use this information to try to explain the diverse phenotypes associated with STXBP1-related disorders. Finally, we will explore current therapies for STXBP1 disorders, including an overview of treatment goals for STXBP1-related disorders, a discussion of the current evidence for therapies, and future directions of personalized medications for STXBP1-related disorders.

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Section: Stxbp1 Physiologic Functionsupporting

confidence: 60%

STXBP1-Related Disorders: Clinical Presentation, Molecular Function, Treatment, and Future Directions

Freibauer,

Wohlleben,

Boelman

2023

Genes

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“…CASK plays not only vital roles in neuron development and synapse vesicle transport but also has essential functions in other organs, especially the vesicle transport function for insulin secrete has been proved associated with CASK [34, 36].…”

Section: Resultsmentioning

confidence: 99%

“…CASK, as a critical synapse scaffold protein, has many binding targets [1,8,13,20,34,36]. For its N-terminal CAMK domain interactions, the CID binding core is essential for all targets [33][34][35]37].…”

Section: Discussionmentioning

confidence: 99%

Crystal Structure of Caskin1/CASK complex reveals the molecular basis of the binding specificity of CASK_CAMK domain and its binding partners

Wang

Chen

Jiang

et al. 2022

Preprint

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CASK is a unique scaffold protein in the synapse system. It links numerous proteins to the pre- or post-synaptic region and is critical to the homeostasis of synaptic vesicles. The N-terminus of CASK is a calcium/calmodulin-dependent protein kinase (CAMK) domain, which has diverse functions and interacts with downstream proteins to form a scaffold platform. Caskin1 is one of the brain-specific adaptor proteins of CASK. Here we crystalized the Caskin1_CASK interaction domain (CID) and CASK_CAMK. Comprehensive X-ray crystallographic study of Caskin1_CID/CASK_CAMK complex and following biochemical/ cell biology experiments uncovered the interaction codes governing CASK_CAMK and its binding partners. Previous studies showed that CASK_CAMK domain interacts with Caskin1 CID domain with relatively low affinity. In this study, we re-visit this interaction by re-mapping the interaction boundary and solving their complex structure. Based on the structure, we systematically compared the interactions between CASK_CAMK and other binding partners. Our results showed that CAMK domain occupy the CID peptide by using its C-lobe groove (between the α1 and α2) and there is a highly conserved signature motif (ζ-x-ψ-W-ψ-x-R) in the CID domain, where ζ is acidic side chain containing residues, x is any amino acid residue, ψ is hydrophobic residues, W is for tryptophan, and R is arginine. These findings allowed us to identify several new potential cytoplasmic binding partners for CASK_CAMK.

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“…Zhang et al, 2017). APBA1 is involved in insulin secretion (K. Zhang et al, 2021). TIMM17B is a protein that mediates inner mitochondrial membrane transport, and it may be related to insulin resistance and obesity in human populations (Dubé et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

A paleogenomic investigation of overharvest implications in an endemic wild reindeer subspecies

Kellner,

Moullec,

Ellegaard

et al. 2023

Preprint

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Overharvest can severely reduce the abundance and distribution of a species and thereby impact its genetic diversity and threaten its future viability. Overharvest remains an ongoing issue for Arctic mammals, which due to climate change now also confront one of the fastest changing environments on Earth. The high-Arctic Svalbard reindeer (Rangifer tarandus platyrhynchus), endemic to Svalbard, experienced a harvest-induced demographic bottleneck that occurred during the 17-20th century. Here we investigate changes in genetic diversity, population structure and gene-specific differentiation during and after this overharvesting event. Using whole-genome shotgun sequencing, we generated the first ancient nuclear (n = 11) and mitochondrial (n = 18) genomes from Svalbard reindeer (up to 4000 BP) and integrated these data with a large collection of modern genome sequences (n = 90), to infer temporal changes. We show that hunting resulted in major genetic changes and restructuring in reindeer populations. Near-extirpation and 400 years of genetic drift have altered the allele frequencies of important genes contributing to diverse biological functions. Median heterozygosity was reduced by 23%, while the mitochondrial genetic diversity was reduced only to a limited extent, likely due to low pre-harvest diversity and a complex post-harvest recolonization process. Such genomic erosion and genetic isolation of populations due to past anthropogenic disturbance will likely play a major role in metapopulation dynamics (i.e., extirpation, recolonization) under further climate change. Our results from a high-arctic case study therefore emphasize the need to understand the long-term interplay of past, current, and future stressors in wildlife conservation.

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CASK, APBA1, and STXBP1 collaborate during insulin secretion

Cited by 8 publications

References 32 publications

STXBP1-Related Disorders: Clinical Presentation, Molecular Function, Treatment, and Future Directions

STXBP1-Related Disorders: Clinical Presentation, Molecular Function, Treatment, and Future Directions

Crystal Structure of Caskin1/CASK complex reveals the molecular basis of the binding specificity of CASK_CAMK domain and its binding partners

A paleogenomic investigation of overharvest implications in an endemic wild reindeer subspecies

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