ライフサイエンスコーパス: piccolo

1 olocalized with another active zone protein, Piccolo.

2 shRNA-mediated knockdown to demonstrate that Piccolo, a multidomain protein of the active zone cytoma

3 Munc13, Rim, Bassoon and Piccolo/Aczonin are recently identified presynaptic cyto

4 We now show that piccolo/aczonin, a recently described active-zone protei

5 Piccolo and bassoon are highly homologous multidomain pr

6 Furthermore, Piccolo and Bassoon are necessary for ELKS2/CAST to leav

7 gi network on a common vesicle that requires Piccolo and Bassoon for its proper assembly.

8 However, core CAZ proteins Piccolo and Bassoon have long been believed exclusive to

9 Thus, we propose that piccolo and bassoon play a redundant role in synaptic ve

10 loss of the presynaptic active zone proteins Piccolo and Bassoon triggers the loss of synaptic vesicl

11 at the destruction of SVs in boutons lacking Piccolo and Bassoon was associated with the induction of

12 Despite a nearly complete loss of piccolo and bassoon, however, we still did not detect an

13 ted presynaptic autophagy in boutons lacking Piccolo and Bassoon, providing insights into the molecul

14 To unmask potentially redundant functions of piccolo and bassoon, we thus acutely knocked down expres

15 homology to vertebrate active zone proteins Piccolo and RIM.

16 nuation of the active-zone proteins Bassoon, Piccolo, and CAST/Erc2.

17 additionally led to loss of Munc13, Bassoon, Piccolo, and RIM-BP, indicating disassembly of the activ

18 presynaptic active zone, including bassoon, piccolo, and RIM1.

19 n electrophysiological phenotype in cultured piccolo- and bassoon-deficient neurons in either GABAerg

20 Bassoon and Piccolo are active zone specific cytosolic proteins esse

21 n the ribbon-associated proteins Bassoon and Piccolo are disrupted, and few intact ribbons are presen

22 nal 165 amino acids of the Yng2 component of Piccolo are sufficient with Esa1 to specifically act on

23 Bassoon and Piccolo are two high molecular weight components of the

24 fied the N-terminal proline-rich Q domain in Piccolo as a region that interferes with clathrin-mediat

25 ngs demonstrate a novel role for Bassoon and Piccolo as critical regulators of presynaptic ubiquitina

26 Our results suggest that Piccolo, as a structural protein of the CAZ, may serve t

27 Our studies show that Piccolo, Bassoon, and ELKS2/CAST exit the trans-Golgi ne

28 nsport of three crucial synaptic components, Piccolo-bassoon Transport Vesicles (PTVs), Synaptic Vesi

29 nalyses reported here also indicate that the Piccolo-Bassoon transport vesicles leaving the Golgi may

30 a sandwiched Bassoon puncta and aligned in a Piccolo-Bassoon-Piccolo structure in adult NMJs.

31 Ca(2+) binds to piccolo by virtue of its C(2)A-domain via an unusual mec

32 he distinct Ca(2+)-binding properties of the piccolo C(2)A- domain are mediated by an evolutionarily

33 The unusual Ca(2+)-binding mode of the piccolo C(2)A-domain reveals that C(2)-domains are mecha

34 The low Ca(2+) affinity of the piccolo C(2)A-domain suggests that piccolo could functio

35 from the Pclo gene, reported to lack >95% of Piccolo, continue to express multiple Piccolo isoforms.

36 ty of the piccolo C(2)A-domain suggests that piccolo could function in short-term synaptic plasticity

37 electrophysiology and electron microscopy of piccolo-deficient synapses failed to uncover a major phe

38 ynaptic vesicle clustering in double bassoon/piccolo-deficient synapses.

39 Our studies define the Piccolo determinants sufficient to assemble its three su

40 its three subunits into a complex as well as Piccolo determinants sufficient to specifically acetylat

41 Work by Piccolo et al. shows that the Tet1 and Tet2 hydroxylases

42 Boutons lacking Piccolo exhibit enhanced activity-dependent Synapsin1a d

43 study, we use interference RNAs to eliminate Piccolo expression from cultured hippocampal neurons to

44 logous protein Bassoon, which indicates that Piccolo has a unique role in coupling the mobilization o

45 -associated protein that is colocalized with Piccolo in nerve terminals of hippocampal primary neuron

46 t and recruitment of the active zone protein Piccolo into nascent synapses.

47 Piccolo is a high molecular weight component of the acti

48 Piccolo is a high molecular weight multi-domain protein

49 alysis of its primary structure reveals that Piccolo is a multidomain zinc finger protein structurall

50 Piccolo is a novel component of the presynaptic cytoskel

51 Our data show that Piccolo is not required for glutamatergic synapse format

52 Our results show that Piccolo is transported to nascent synapses on an approxi

53 95% of Piccolo, continue to express multiple Piccolo isoforms.

54 Here, we generated piccolo knockin/knockout mice that either contain wild-t

55 olo mutant mice were viable and fertile, but piccolo knockout mice exhibited increased postnatal mort

56 down expression of bassoon in wild-type and piccolo knockout neurons.

57 uncated (partial knockout), or <5% levels of piccolo (knockout).

58 Loss of Bassoon and Piccolo leads to the aberrant degradation of multiple pr

59 In contrast, the Piccolo levels in NMJs from aged mice were comparable to

60 d for new genetic models with which to study Piccolo loss of function.

61 These features indicate that Piccolo may act to scaffold proteins involved in synapti

62 All piccolo mutant mice were viable and fertile, but piccolo

63 t least two multiprotein complexes, NuA4 and Piccolo NuA4 (picNuA4), and its essential function is be

64 , Ybf2/Sas3, Sas2, Tip60 family HAT complex, Piccolo NuA4 (picNuA4).

65 this cysteine (C304A) in Esa1 or within the piccolo NuA4 complex yielded an enzyme that was catalyti

66 Widom 601" sequence were acetylated with the Piccolo NuA4 complex, which acetylates mainly H4 N-termi

67 suggest that the acetylation of histones by Piccolo NuA4 disturbs not only the structure of a nucleo

68 the Esa1-containing Saccharomyces cerevisiae Piccolo NuA4 histone acetyltransferase complex.

69 histone H4, and also to nucleosomal DNA when Piccolo NuA4 interacts with the nucleosome.

70 Piccolo NuA4 is an essential yeast histone acetyltransfe

71 ce neither region identified is required for Piccolo NuA4 to bind to nucleosomes and yet both are nee

72 mology domain of Epl1 play critical roles in Piccolo NuA4's ability to act on the nucleosome.

73 While Piccolo NuA4's catalytic subunit Esa1 alone is unable to

74 member Esa1, and its physiological complex (piccolo NuA4), steady-state kinetic analyses revealed a

75 sitively regulate the activities of NuA4 and Piccolo NuA4.

76 indicate the encoded proteins may represent Piccolo orthologs.

77 aptic active zone, such as bassoon (BSN) and piccolo (PCLO).

78 These data suggest that Piccolo plays a role in the trafficking of synaptic vesi

79 omains that resemble the PXXP motif of human Piccolo proteins, which bind SH3 domains in proteins inv

80 Piccolo puncta sandwiched Bassoon puncta and aligned in

81 Utilizing the Piccolo Q domain as bait in a yeast two-hybrid screen, w

82 reactive for presynaptic proteins, including piccolo, Rab3C, vesicular glutamate transporter 2, and c

83 These data reveal that Piccolo regulates neurotransmitter release by facilitati

84 Our data demonstrate the conservation of a Piccolo-related protein in invertebrates and identify cr

85 We previously identified Drosophila Piccolo-RIM-related Fife, which regulates neurotransmiss

86 Here, we present the identification of a piccolo-rim-related gene in invertebrates, together with

87 e Esa1 chromodomain plays a critical role in Piccolo's ability to distinguish between histones and nu

88 soon puncta and aligned in a Piccolo-Bassoon-Piccolo structure in adult NMJs.

89 ckin), approximately 60% decreased levels of piccolo that is C-terminally truncated (partial knockout

90 owever, the chromodomain is not required for Piccolo to bind to nucleosomes, suggesting a role for th

91 Results: Of the 696 PICCOLO trial patients in the irinotecan-vs-irinotecan w

92 anned retrospective biomarker study from the PICCOLO trial, which tested the addition of panitumumab

93 at either contain wild-type levels of mutant piccolo unable to bind Ca(2+) (knockin), approximately 6

94 Siah1, an interacting partner of Bassoon and Piccolo whose activity is negatively regulated by their

95 tecan, and ciclosporin in colorectal cancer (PICCOLO) with with the a priori hypothesis that high tum

96 The Piccolo zinc fingers were found to interact with the dua