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Bassoon speeds vesicle reloading at a central excitatory synapse

Bassoon speeds vesicle reloading at a central excitatory synapse. S. Hallermann et al, 2010. from S. Hallermann et al, 2010. Conventional synapse Ribbon synapse. Adapted from Christina Joselevitch and David Zenisek , 2010.

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Bassoon speeds vesicle reloading at a central excitatory synapse

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  1. Bassoonspeedsvesiclereloading at a central excitatorysynapse S. Hallermann et al, 2010

  2. from S. Hallermann et al, 2010

  3. ConventionalsynapseRibbonsynapse Adaptedfrom Christina Joselevitch and David Zenisek, 2010 Conventinalsynapse are composed of anaggregate of SVscontaining NT in closeappositiontothe PSD Ribbonsynapses (found in photoreceptors, bipolar cells, sensoryhaircells) display in additionpresynapticribbons , whichtethersynapticvesiclesclosetotherelasesite Despitethemorphologicaldiferences, the CAZ proteins in bothsynapses are thesame from Christina Joselevitch and David Zenisek, 2010

  4. There are FIVE proteinfamilieshighlyenriched in the CAZ (cytomatrix of Azs) Munc 13s RIMs ELKS/CAST proteins Piccolo and Bassoon α-liprins BASSOON- largecoiled-coilprotein, 4000aa (≈ 40kDa) - enriched in CAZ of exictatory and inhibitorysynapses In Ribbonsynapses, thedeletion of exon 4 and 5 of Bassoon gene leads todisruptedassembly of AZ cytomatrix and impairedauditorysignaling from S. Hallermann et al, 2010

  5. Role of Bassoon at AZs Suggestthatbassoonisimportantforvesiclecycle Doesbassoonplaythesame role everywhere? from Christina Joselevitch and David Zenisek, 2010

  6. Bassoonspeeds up refilling • Frank et al, 2010 and Hallermann et al, 2010 investigatethe role of bassoon in onesynapsethatcontainsribbon and onethatdoesnot. Parallels and differenceswerefoundregardingbassoonfunction in thesetwo presynaptic environmentsthatsuggeststhattheproteins has multiplefunctions from Christina Joselevitch and David Zenisek, 2010

  7. Bassoon role wasinvetigatedthroughgeneration of bassoonmutantmice and comparingwith wild-typeanimals Mutants BsnΔEx4/5 a central part of bassoonprotein has ben deletedleadingtoexpression of anincompleteproteinfragment (Altrock et al., 2003) Bsngt, the gene istrapped in intron 1-2 (Hallerman et al., 2010) Usingthesetwomutants of thebassoondisruption , wasinvestigatedtheeffectson thesynaptictransmission in haircells (containingribbonstructures) and cerebellar Mossyfibersto granule cell (MF-GC) synapse.

  8. Suggests a defect in fastrefilling Intactslowermechanism of recoveryfromdepressionthatwascapable of refillingthevesicle pool at longer time intervals BUT in 2003 itwasfoundthatthereiswas a near normal recoveryfrompaired pulse depression in culture and acute hippocampal preparation, whichmeansthatthesetworesults are in contrast Question: Why some synapses exhibit profound defects in recovery from synaptic depression (hair cells, MF-GC), while other preparations do not (hippocampalpreparation) do not? from Christina Joselevitch and David Zenisek, 2010

  9. Question: Why some synapses exhibit profound defects in recovery from synaptic depression (hair cells, MF-GC), while other preparations do not (hippocampalpreparation) do not? Possibleanswer: Themechanismaffectedbybassoonmutationsisonlyused at synapseswherereleaseprobabilityishigh and fastreplenishementisnecessarytokeep up with he demands of thesynapse. In this case bothhaircells and MF-GC exhibithighreleaseprobability and afterexperiments done byHallermann and coworkers, itwasshowedthatthereduction of extracellularcalciumconcentrationto reduce releaseprobabilitylessentheeffects of bassoonabsence. Becausebassooninteractswithmanypartners at AZsitmaybe a aprofound and non-specificsynaptictransmissiondefects in thesemutants. In MF-GC thekinatecorsize of basal transmssion, vesicle pool size, and releaseprobability are unchangedwhile in haircellsynapsethe RRP issubstantiallydiminished. BASSOON AFFECTS REFILLING DIRECTLY OR INDIRECTLY?

  10. Depending on the type of synapse, the involvement of bassoon with Ca2+ channels seems to vary

  11. Because of heterogeneity of effects observed in bassoon mutant synapses the conclusion is that: • different synapses are variable in molecular composition • synapses are different in the role of each component of vesicle cycling • Synapses look different... SO, it might be that at some synapses bassoon has additional functions • eg. at ribbon synapses bassoon might be crucial for the stability of the • ribbon structure • at conventional synapse bassoon absence seems to have no effect for • vesicle docking or holding the CAZ together (because ribbon structure • is absent

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