Biomedical subjects

Fabienne Paumet

Publications and source records attributed to Fabienne Paumet.

6 recordsLinked to original sources

PubMed2007

Selective activation of cognate SNAREpins by Sec1/Munc18 proteins.

Sec1/Munc18 (SM) proteins are required for every step of intracellular membrane fusion, but their molecular mechanism of action has been unclear. In this work, we demonstrate a fundamental role of the SM protein: to act as a stimulatory subunit of its cognate SNARE fusion machinery. In a reconstituted system, mammalian SNARE pairs assemble between bilayers to drive a basal fusion reaction. Munc18-1/nSec1, a synaptic SM protein required for neurotransmitter release, strongly accelerates this reaction through direct contact with both t- and v-SNAREs. Munc18-1 accelerates fusion only for the cognate SNAREs for exocytosis, therefore enhancing fusion specificity.

Amino Acid Motifs↗

PubMed2005

Concerted auto-regulation in yeast endosomal t-SNAREs.

In yeast, the assembly of the target (t)-SNAREs [Tlg2p/Tlg1p,Vti1p] and [Pep12p/Tlg1p,Vti1p] with the vesicular (v)-SNARE Snc2p promotes endocytic fusion. Here, selected mutations and truncations of SNARE proteins were tested in an in vitro fusion assay to identify potential regulatory regions in these proteins, and two distinct regions were found. The first is represented by the combined effect of the three t-SNARE N-terminal regions and the second is located within the Tlg1p SNARE motif. These internal controls provide a potential mechanism to enable SNARE-dependent fusion to be regulated.

Amino Acid Motifs↗

PubMed2004

The specificity of SNARE-dependent fusion is encoded in the SNARE motif.

Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins constitute the core of the fusion machinery, and isolated SNAREs fuse membranes with exquisite specificity by cognate pairing. Most SNAREs have a membrane-spanning region, an N-terminal domain, and a membrane proximal SNARE motif domain. Although the SNARE motif is critical for SNARE complex formation, is it the sole determinant of the specificity of SNARE-dependent fusion? To test this, we make use of a SNARE complex functioning in the late endosomal compartment in yeast. Studying this complex and the previously identified early endosomal SNARE complex, we find that the specificity of fusion resides in the SNARE motifs.

Amino Acid Motifs↗

PubMed2003

i-SNAREs: inhibitory SNAREs that fine-tune the specificity of membrane fusion.

A new functional class of SNAREs, designated inhibitory SNAREs (i-SNAREs), is described here. An i-SNARE inhibits fusion by substituting for or binding to a subunit of a fusogenic SNAREpin to form a nonfusogenic complex. Golgi-localized SNAREs were tested for i-SNARE activity by adding them as a fifth SNARE together with four other SNAREs that mediate Golgi fusion reactions. A striking pattern emerges in which certain subunits of the cis-Golgi SNAREpin function as i-SNAREs that inhibit fusion mediated by the trans-Golgi SNAREpin, and vice versa. Although the opposing distributions of the cis- and trans-Golgi SNAREs themselves could provide for a countercurrent fusion pattern in the Golgi stack, the gradients involved would be strongly sharpened by the complementary countercurrent distributions of the i-SNAREs.

Binding Sites↗

PubMed2002

SNAREs and associated regulators in the control of exocytosis in the RBL-2H3 mast cell line.

Mast cells participate in inflammation and allergies by releasing biologically active mediators stored in numerous cytoplasmic granules. Degranulation is tightly controlled and requires activation of cell surface receptors, such as the high affinity IgE receptor (FcepsilonRI). Here, we discuss some of the key components of the molecular machinery that regulates the final steps of fusion between the granular and plasma membrane based on results obtained with the rat mast cell line RBL-2H3. We emphasize the role of soluble N-ethylmaleimide attachment protein receptors (SNAREs) proteins such as syntaxin 4 that can promote membrane fusion through formation of a stable complex with SNAP-23. We also highlight the role of a Ser/Thr kinase found to be associated with Rab3D, a negative regulator of degranulation. Associated kinase activity, which diminishes after stimulation as a consequence of intracellular calcium increases, specifically phosphorylates syntaxin 4 thereby affecting its capacity to bind to its t-SNARE partner SNAP-23. Our results suggest a new way of how Rab3 GTPases may intersect with the function of SNAREs thought to be universal mediators of membrane fusion.

Animals↗

PubMedDate not supplied

[Cell fusion].

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Animals↗