Syntaxins are a family of

membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. B ...

integrated

Q-SNARE SNARE proteins – " SNAP REceptor" – are a large protein family consisting of at least 24 members in yeasts, more than 60 members in mammalian cells, and some numbers in plants. The primary role of SNARE proteins is to mediate vesicle fu ...

proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

participating in

exocytosis Exocytosis () is a form of active transport and bulk transport in which a cell transports molecules (e.g., neurotransmitters and proteins) out of the cell ('' exo-'' + ''cytosis''). As an active transport mechanism, exocytosis requires the use o ...

Domains

Syntaxins possess a single C-terminal transmembrane domain, a SNARE domain (known as H3), and an N-terminal regulatory domain (Habc). Syntaxin 17 may have two transmembrane domains. * The SNARE (H3) domain binds to both

synaptobrevin Synaptobrevins (''synaptobrevin isotypes 1-2'') are small integral membrane proteins of secretory vesicles with molecular weight of 18 kilodalton (kDa) that are part of the vesicle-associated membrane protein (VAMP) family. Synaptobrevi ...

and

SNAP-25 Synaptosomal-Associated Protein, 25kDa (SNAP-25) is a Target Soluble NSF (''N''-ethylmaleimide-sensitive factor) Attachment Protein Receptor (t-SNARE) protein encoded by the ''SNAP25'' gene found on chromosome 20p12.2 in humans. SNAP-25 is a comp ...

forming the core SNARE complex. Formation of this stable SNARE core complex is believed to generate the free energy required to initiate fusion between the vesicle membrane and plasma membrane. * The N-terminal Habc domain is formed by 3 α-helices and when collapsed onto its own H3 helix forms an inactive "closed" syntaxin conformation. This closed conformation of syntaxin is believed to be stabilized by binding of

Munc-18 Munc-18 (an acronym for mammalian uncoordinated-18) proteins are the mammalian homologue of UNC-18 (which was first discovered in the nematode worm C. elegans) and are a member of the Sec1/Munc18-like (SM) protein family. Munc-18 proteins have been ...

(nSec1), although more recent data suggests that nSec1 may bind to other conformations of syntaxin, as well. The "open" syntaxin conformation is the conformation that is competent to form into SNARE core complexes.

Function

''In vitro'' syntaxin per se is sufficient to drive spontaneous calcium independent fusion of

synaptic vesicles In a neuron, synaptic vesicles (or neurotransmitter vesicles) store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impul ...

containing v-SNAREs. More recent and somewhat controversial amperometric data suggest that the transmembrane domain of Syntaxin1A may form part of the fusion pore of exocytosis.

Binding

Syntaxins bind

synaptotagmin Synaptotagmins (SYTs) constitute a family of membrane-trafficking proteins that are characterized by an N-terminal transmembrane region (TMR), a variable linker, and two C-terminal C2 domains - C2A and C2B. There are 17 isoforms in the mammalian s ...

in a calcium-dependent fashion and interact with voltage dependent calcium and potassium channels via the C-terminal H3 domain. Direct syntaxin-channel interaction is a suitable molecular mechanism for proximity between the fusion machinery and the gates of Ca²⁺ entry during depolarization of the presynaptic axonal boutons. The Sec1/Munc18 protein family is known to bind to Syntaxin and regulate Syntaxins machinery. Munc18-1 binds to Syntaxin 1A via two distinct sites referred as

N-terminus The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...

binding and "closed" conformation that incorporates both the central Habc domain and the SNARE core domain. Munc18-1 binding to the N-terminus of Syntaxin-1 is thought to facilitate Syntaxin-1 interaction with another SNARE, while binding to the "closed" conformation of Syntaxin-1 is believed to be inhibitory. Recently published data show that alternative spliced Syntaxin 1 (STX1B) which lacks the transmembrane domain localizes in the nuclei.

Genes

Human genes encoding syntaxin proteins include: *

STX1A Syntaxin-1A is a protein that in humans is encoded by the ''STX1A'' gene. Function Synaptic vesicles store neurotransmitters that are released during calcium-regulated exocytosis. The specificity of neurotransmitter release requires the local ...

STX1B Syntaxin-1B is a protein that in humans is encoded by the ''STX1B'' gene. Interactions STX1B has been shown to interact with UNC13B Protein unc-13 homolog B is a protein that in humans is encoded by the ''UNC13B'' gene. Function This g ...

, STX2, STX3,

STX4 Syntaxin-4 is a protein that in humans is encoded by the ''STX4'' gene. Interactions STX4 has been shown to interact with: * Gelsolin, * NAPA, * RAB4A, * SNAP-25, * SNAP23, * STXBP1, * STXBP5, * Syntaxin binding protein 3, * TXLNB, ...

STX5 Syntaxin-5 is a protein that in humans is encoded by the ''STX5'' gene. Interactions STX5 has been shown to interact with: * BET1L, * GOSR1, * GOSR2, * NAPA, and * USO1 General vesicular transport factor p115 is a protein that in human ...

, STX6, STX7,

STX8 Syntaxin-8 is a protein that in humans is encoded by the ''STX8'' gene. Syntaxin 8 directly interacts with HECTd3 and has similar subcellular localization. The protein has been shown to form the SNARE complex with syntaxin 7, vti1b and endobre ...

, * STX10, STX11, STX12,

STX16 Syntaxin-16 is a protein that in humans is encoded by the ''STX16'' gene. It has been associated with pseudohypoparathyroidism type Ib. Losing this gene causes loss of methylation at GNAS1 exon A/B. Interactions STX16 has been shown to inter ...

, STX17, STX18, STX19

References

External links