Alpha-latrotoxin

The best-studied latrotoxin is alpha-latrotoxin, which acts presynaptically to release neurotransmitterscite journal |author=Khvotchev M, Südhof TC |title=alpha-latrotoxin triggers transmitter release via direct insertion into the presynaptic plasma membrane |journal=EMBO J. |volume=19 |issue=13 |pages=3250–62 |year=2000 |month=July |pmid=10880438 |pmc=313948 |doi=10.1093/emboj/19.13.3250 |url=http://dx.doi.org/10.1093/emboj/19.13.3250] from sensory and motor neurons, as well as on endocrine cells (to release insulin, for example). [cite journal |author=Südhof TC |title=alpha-Latrotoxin and its receptors: neurexins and CIRL/latrophilins |journal=Annu. Rev. Neurosci. |volume=24 |issue= |pages=933–62 |year=2001 |pmid=11520923 |doi=10.1146/annurev.neuro.24.1.933 |url=http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.neuro.24.1.933?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dncbi.nlm.nih.gov] It is a ~130 kDa proteincite journal |author=Ushkaryov YA, Rohou A, Sugita S |title=alpha-Latrotoxin and its receptors |journal=Handb Exp Pharmacol |volume= |issue=184 |pages=171–206 |year=2008 |pmid=18064415 |doi=10.1007/978-3-540-74805-2_7 |url=http://dx.doi.org/10.1007/978-3-540-74805-2_7] which exists mainly in its dimerized or tetramerized forms.

Mechanism of action

Pore formation

α-latrotoxin tetramers can form ion-permeable pores in the membrane of target cells, causing influx of calcium ions and thus leading to massive neurotransmitter release. Eventually, the cellular membrane can be disrupted, leading to cell death Fact|date=July 2008.The insertion of α-latrotoxin into artificial membranes is a rare event, and it is only when specific receptors are present on the surface of biological membranes that membrane insertion occurs efficiently.

Membrane penetration

Although tetrameric pore formation of α-latrotoxin has been shown conclusively Fact|date=July 2008, some authors still dispute whether this is the main mode of action of α-latrotoxin, and believe that α-latrotoxin (tetrameric or not) may penetrate through the membrane of target cells to interact directly with intracellular neurotransmitter release machinery. Fact|date=July 2008

Receptors

Three receptors for α-latrotoxin have been described:
* neurexin
* latrophilin (aka CIRL, Calcium-Independent Receptor for Latrophilin)
* protein tyrosine phosphatase sigma (PTPσ).

It is the expression patterns of these receptors which confers specificity to α-latrotoxin. So far, only latrophilin has been shown to be able to signal. In addition, because of its ability to bind α-latrotoxin in the absence of calcium, it may be involved in the intriguing and unexplained calcium-independent actions of α-latrotoxin. Fact|date=July 2008 A secretory cell that is not sensitive to α-latrotoxin has yet to be found [α-Latrotoxin and Its ReceptorsYuri A. Ushkaryov, Alexis Rohou, and Shuzo Sugita PMCID: PMC2519134UKMSID: UKMS2214]

ignaling

As well as the major effects of α-latrotoxin pore formation, other effects of α-latrotoxin are mediated by interaction with latrophilin and intracellular signalling (see signal transduction). Fact|date=July 2008

References

External links

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*α-Latrotoxin and Its ReceptorsYuri A. Ushkaryov, Alexis Rohou, and Shuzo SugitaPMCID: PMC2519134UKMSID: UKMS2214http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=18064415