NDLI: Regulation of Podosome Formation in Macrophages by a Splice Variant of the Sodium Channel SCN8A * S⃞

Content Provider	PubMed Central
Author	Carrithers, Michael D. Chatterjee, Gouri Carrithers, Lisette M. Offoha, Roosevelt Uzoma, Iheagwara Rahner, Christoph Graham, Morven Waxman, Stephen G.
Abstract	Voltage-gated sodium channels initiate electrical signaling in excitable cells such as muscle and neurons. They also are expressed in non-excitable cells such as macrophages and neoplastic cells. Previously, in macrophages, we demonstrated expression of SCN8A, the gene that encodes the channel NaV1.6, and intracellular localization of NaV1.6 to regions near F-actin bundles, particularly at areas of cell attachment. Here we show that a splice variant of NaV1.6 regulates cellular invasion through its effects on podosome and invadopodia formation in macrophages and melanoma cells. cDNA sequence analysis of SCN8A from THP-1 cells, a human monocyte-macrophage cell line, confirmed the expression of a full-length splice variant that lacks exon 18. Immunoelectron microscopy demonstrated NaV1.6-positive staining within the electron dense podosome rosette structure. Pharmacologic antagonism with tetrodotoxin (TTX) in differentiated THP-1 cells or absence of functional NaV1.6 through a naturally occurring mutation (med) in mouse peritoneal macrophages inhibited podosome formation. Agonist-mediated activation of the channel with veratridine caused release of sodium from cationic vesicular compartments, uptake by mitochondria, and mitochondrial calcium release through the Na/Ca exchanger. Invasion by differentiated THP-1 and HTB-66 cells, an invasive melanoma cell line, through extracellular matrix was inhibited by TTX. THP-1 invasion also was inhibited by small hairpin RNA knockdown of SCN8A. These results demonstrate that a variant of NaV1.6 participates in the control of podosome and invadopodia formation and suggest that intracellular sodium release mediated by NaV1.6 may regulate cellular invasion of macrophages and melanoma cells.
Related Links	http://dx.doi.org/10.1074/jbc.M801892200
Starting Page	8114
File Format	PDF
ISSN	1083351X
e-ISSN	1083351X
Journal	The Journal of Biological Chemistry
Issue Number	12
Volume Number	284
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2009-03-20
Access Restriction	Open
Rights Holder	American Society for Biochemistry and Molecular Biology
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Regulation of Podosome Formation in Macrophages by a Splice Variant of the Sodium Channel SCN8A

Regulation of podosome formation in macrophages by a splice variant of the sodium channel SCN8A.

A novel SCN8A variant of unknown significance in pediatric epilepsy: a case report

Regulation of the Epithelial Na+ Channel by the Protein Kinase CK2* S⃞

Selective Expression in Carotid Body Type I Cells of a Single Splice Variant of the Large Conductance Calcium- and Voltage-activated Potassium Channel Confers Regulation by AMP-activated Protein Kinase*

Interaction of Voltage-gated Sodium Channel Nav1.6 (SCN8A) with Microtubule-associated Protein Map1b*

FBP17 Mediates a Common Molecular Step in the Formation of Podosomes and Phagocytic Cups in Macrophages* S⃞

An Obligatory Heterodimer of 14-3-3β and 14-3-3ε Is Required for Aldosterone Regulation of the Epithelial Sodium Channel* S⃞

Dysfunction of the Scn8a Voltage-gated Sodium Channel Alters Sleep Architecture, Reduces Diurnal Corticosterone Levels, and Enhances Spatial Memory*

Regulation of Podosome Formation in Macrophages by a Splice Variant of the Sodium Channel SCN8A * S⃞

Similar Documents

Regulation of Podosome Formation in Macrophages by a Splice Variant of the Sodium Channel SCN8A

Regulation of podosome formation in macrophages by a splice variant of the sodium channel SCN8A.

A novel SCN8A variant of unknown significance in pediatric epilepsy: a case report

Regulation of the Epithelial Na+ Channel by the Protein Kinase CK2* S⃞

Selective Expression in Carotid Body Type I Cells of a Single Splice Variant of the Large Conductance Calcium- and Voltage-activated Potassium Channel Confers Regulation by AMP-activated Protein Kinase*

Interaction of Voltage-gated Sodium Channel Nav1.6 (SCN8A) with Microtubule-associated Protein Map1b*

FBP17 Mediates a Common Molecular Step in the Formation of Podosomes and Phagocytic Cups in Macrophages* S⃞

An Obligatory Heterodimer of 14-3-3β and 14-3-3ε Is Required for Aldosterone Regulation of the Epithelial Sodium Channel* S⃞

Dysfunction of the Scn8a Voltage-gated Sodium Channel Alters Sleep Architecture, Reduces Diurnal Corticosterone Levels, and Enhances Spatial Memory*

Regulation of Podosome Formation in Macrophages by a Splice Variant of the Sodium Channel SCN8A * S⃞