PXD049433

PXD049433 is an original dataset announced via ProteomeXchange.

Title	Proximity labeling proteomics reveals Kv1.3 potassium channel immune interactors in microglia.
Description	Microglia are resident immune cells of the brain and regulate its inflammatory state. In neurodegenerative diseases, microglia transition from a homeostatic state to a state referred to as disease associated microglia (DAM). DAM express higher levels of proinflammatory signaling molecules, like STAT1 and TLR2, and show transitions in mitochondrial activity toward a more glycolytic response. Inhibition of Kv1.3 decreases the proinflammatory signature of DAM, though how Kv1.3 influences the response is unknown. Our goal was to establish the potential proteins interacting with Kv1.3 during transition to DAM. We utilized TurboID, a biotin ligase, fused to Kv1.3 to evaluate the potential interacting proteins with Kv1.3 via mass spectrometry in BV-2 microglia following TLR4-mediated activation. Electrophysiology, western blotting, and flow cytometry were used to evaluate Kv1.3 channel presence and TurboID biotinylation activity. We hypothesized that Kv1.3 contains domain-specific interactors that vary during a TLR4-induced inflammatory response, some of which are dependent on the PDZ-binding domain on the C-terminus. We determined that the N-terminus of Kv1.3 is responsible for trafficking Kv1.3 to the cell surface and mitochondria (e.g. NUNDC, TIMM50). Whereas, the C-terminus interacts with immune signaling proteins in an LPS-induced inflammatory response (e.g. STAT1, TLR2, and C3). There are 70 proteins that rely on the C-terminal PDZ-binding domain to interact with Kv1.3 (e.g. ND3, Snx3, and Sun1). Overall, we highlight that the Kv1.3 potassium channel functions beyond conducting the outward flux of potassium ions in an inflammatory context and that KV1.3 modulates activity of key immune signaling proteins, such as STAT1 and C3
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:38:18.220.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	UPASNA SRIVASTAVA
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-16 14:13:30	ID requested
1	2024-05-06 07:54:24	announced
⏵ 2	2024-10-22 06:38:18	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Proximity labeling,Neurodegeneration, Neuroinflammation, Kv1.3 potassium channel, Microglia

Christine Bowen
contact affiliation	PhD student, Department of Biochemistry, Emory University
contact email	cbowen8@emory.edu
lab head
UPASNA SRIVASTAVA
contact affiliation	YALE UNIVERSITY
contact email	upasna.srivastava@yale.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD049433
     1. Label: PRIDE project
     2. Name: Proximity labeling proteomics reveals Kv1.3 potassium channel immune interactors in microglia.