Neuregulin-1 proteins in rat brain and transfected cells are localized to lipid rafts.
Neuregulin-1 proteins and their receptors, which are members of the ErbB subfamily of receptor tyrosine kinases, play essential roles in the development of the nervous system and heart. Most neuregulin-1 isoforms are synthesized as transmembrane proproteins that are proteolytically processed to yield an N-terminal fragment containing the bioactive EGF-like domain. In this study we investigated whether neuregulins are found in lipid rafts, membrane microdomains hypothesized to have important roles in signal transduction, protein trafficking, and proteolytic processing. We found that 45% of a 140-kDa neuregulin protein in rat brain synaptosomal plasma membrane fractions was insoluble in 1% Triton X-100. Flotation gradient analysis demonstrated the presence of the brain 140 kDa neuregulin protein in low-density fractions enriched in PSD-95, a known lipid raft protein. In transfected cells expressing the neuregulin I-beta 1a or the III-beta 1a isoform, most of the neuregulin proprotein was insoluble in 1% Triton X-100, and neuregulin proproteins and C-terminal fragments were detected in lipid raft fractions. In contrast, the III-beta 1a N-terminal fragment was detected only in the detergent-soluble fraction. These results suggest that localization of neuregulins to lipid rafts may play a role in neuregulin signaling within the nervous system.
Department of Biology, Emory University, Atlanta, Georgia, USA.
K E
KE
Frenzel
D L
DL
Falls
D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry; D016466:CHO Cells; D002458:Cell Fractionation; D006224:Cricetinae; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D021962:Membrane Microdomains / Q000737:chemistry*; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins / Q000737:chemistry; D020890:Neuregulin-1 / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D017830:Octoxynol / Q000737:chemistry / Q000494:pharmacology; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D015398:Signal Transduction / Q000502:physiology; D012995:Solubility / Q000187:drug effects; D013347:Subcellular Fractions / Q000737:chemistry; D013570:Synaptic Membranes / Q000737:chemistry; D013574:Synaptosomes / Q000737:chemistry; D014162:Transfection
D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; D020033:Protein Isoforms; D011994:Recombinant Proteins; C033652:postsynaptic density proteins; D017830:Octoxynol