ライフサイエンスコーパス: TMEM16

1 pH was observed in the wild-type, but not in tmem16(-/-) .

2 ) mutants, but unaffected in almt12(-/-) and tmem16(-/-) .

3 mber), and increased sodium tolerance (yeast TMEM16).

4 ce at the dimer-dimer interface in mammalian TMEM16s.

5 ix in TM4 to structure-function relations in TMEM16 and the related OSCA/TMEM63 family, further highl

6 lso expressed in these cells, while TMEM16B, TMEM16D and TMEM16E were all at least 50 times less abun

7 OSCAs and related TMEM16s and transmembrane channel-like (TMC) proteins fo

8 echanisms that may be shared by OSCA/TMEM63, TMEM16, and TMC channels.

9 ther family members, such as TMEM16C (ANO3), TMEM16D (ANO4), TMEM16F (ANO6), TMEM16G (ANO7) and TMEM1

10 The recently identified TMEM16/anoctamin protein family includes Ca(2+)-activate

11 Here, we show that the TMEM16/anoctamins subdued and white walker (wwk; CG15270

12 Several chloride channels including TMEM16, bestrophin, CFTR, CLCN2 and CLCA1, are also expr

13 TMEM16 Ca(2+)-activated phospholipid scramblases (CaPLSa

14 We conclude that TMEM16 CaCCs have intrinsic Vm - and Cl(-) -sensitive du

15 ine-binding probe commonly used to report on TMEM16 CaPLSase activity.

16 are necessary in future endeavors to develop TMEM16 CaPLSase inhibitors.

17 idate the gating and permeation mechanism of TMEM16 CaPLSases and channels.

18 Pharmacological tools specifically targeting TMEM16 CaPLSases are urgently needed to understand these

19 erstanding of TMEM16 proteins, how mammalian TMEM16 CaPLSases open and close, or gate their phospholi

20 he structural basis of anion conduction in a TMEM16 channel and it defines the foundation for the div

21 sights into the mechanistic understanding of TMEM16 channel gating and lipid-dependent regulation.

22 d suppress expression of subdued (encoding a TMEM16 channel).

23 Two other purified TMEM16-channel homologues do not mediate scrambling, sug

24 TMEM16 channels consist of eight putative transmembrane

25 The role of the putative pore-loop of TMEM16 channels was investigated using a chimeric approa

26 Given the physiological importance of TMEM16 channels, it is important to study how incoming s

27 ng and validated the idea that ions permeate TMEM16 Cl(-) channels via a structurally homologous path

28 ts, the anoctamin family (ANO, also known as TMEM16) exhibits characteristics most similar to those e

29 Our finding that Subdued is a moonlighting TMEM16 expands our understanding of the molecular mechan

30 Whether distant relatives of the vertebrate TMEM16 families also form CaCCs is an intriguing open qu

31 dentify a molecular link between the ORP and TMEM16 families and a role for endocytosis of PS in PE s

32 elated calcium-activated ion channels in the TMEM16 family and conducting systematic mutagenesis of a

33 The TMEM16 family comprises Ca(2+)-activated Cl(-) channels

34 and SCN2A (rs3769955: P = 3.1 x 10(-10)), a TMEM16 family gene (ANO3; rs114444506: P = 3.7 x 10(-20)

35 Members of the TMEM16 family have either lipid scramblase or chloride c

36 Here we report that a TMEM16 family member from Drosophila melanogaster, Subdu

37 EM16E), aberrant X segregation (a Drosophila TMEM16 family member), and increased sodium tolerance (y

38 s mutant, the first knockout of a vertebrate TMEM16 family member, provides a mouse model of tracheom

39 less abundantly expressed and the remaining TMEM16 family members were absent.

40 We identified 2 TMEM16 family members, TMEM16F and its closest paralog,

41 scramblase or an ion channel like other ANO/TMEM16 family members.

42 Thus, the TMEM16 family might have diverged in two or three differ

43 The TMEM16 family of "transmembrane proteins with unknown fu

44 Recently, members of the TMEM16 family of Ca(2+)-gated channels have been shown t

45 The TM domain is structurally related to the TMEM16 family of calcium-dependent ion channels and lipi

46 The Ca(2+)-activated TMEM16 family of membrane proteins plays an important ro

47 The TMEM16 family of membrane proteins, also known as anocta

48 We find that these channels in the TMEM16 family share a homodimeric architecture facilitat

49 TMEM16F of the TMEM16 family that includes TMEM16A/B Ca(2+)-activated C

50 underlies the evolutionary divergence of the TMEM16 family, and that other homologues, such as TMEM16

51 chemistry facilitate lipid permeation in the TMEM16 family, and we hypothesize that membrane interact

52 TMEM16C belongs to the TMEM16 family, which includes the Ca(2+)-activated Cl(-)

53 n for the diverse functional behavior in the TMEM16 family.

54 rily conserved biophysical properties in the TMEM16 family.

55 Transmembrane protein 16 (TMEM16) family members play numerous important physiolog

56 The transmembrane protein 16 (TMEM16) family of membrane proteins includes both lipid

57 emain to be elucidated and the links between TMEM16 functions and human physiology and pathologies ne

58 Other members of the Tmem16 gene family, including Tmem16f and Tmem16k, were

59 n was significantly reduced by depleting the TMEM16-homolog ANOH-2.

60 d-synaptotagmin homologues Tcb1/2/3, and the TMEM16 homologue Ist2.

61 The recent identification of an ancestral TMEM16 homologue with intrinsic channel and scramblase a

62 gated channel, with characteristics of other TMEM16 homologues, and a Ca(2+)-dependent scramblase, wi

63 -lipid interactions for fungal and mammalian TMEM16s, in both open (Ca(2+)-bound) and closed (Ca(2+)-

64 The TMEM16 inhibitor benzbromarone prevented PS externalizat

65 tion of TMEM16E or TMEM16F or treatment with TMEM16 inhibitors prevented PS externalization and reduc

66 Our findings show specificity in CLCA/TMEM16 interactions and suggest broad physiological and

67 roteins in yeast: Ist2 (related to mammalian TMEM16 ion channels), the tricalbins (Tcb1/2/3, ortholog

68 mputational study of lipid scrambling by all TMEM16 members with experimentally solved structures.

69 However, most TMEM16 members, including TMEM16F, maintain an additiona

70 structure of the fungal Nectria haematococca TMEM16 (nhTMEM16) scramblase suggested a putative mechan

71 oroughly characterized Subdued, a Drosophila TMEM16 ortholog.

72 TMEM16 phospholipid scramblases may be a therapeutic tar

73 unctional pairing between two other CLCA and TMEM16 protein family members, namely CLCA4 and the CaCC

74 conformations of the groove are observed in TMEM16 protein structures, but how these conformations f

75 ctamin 1), a member of the transmembrane 16 (TMEM16) protein family, forms CaCCs in pulmonary artery

76 The calcium-activated TMEM16 proteins and the mechanosensitive/osmolarity-acti

77 understanding of the molecular mechanisms of TMEM16 proteins and their evolution and physiology in bo

78 Anoctamin (ANO)/TMEM16 proteins exhibit diverse functions in cells throu

79 nd the biological functions of the enigmatic TMEM16 proteins in different organisms, here, by combini

80 sults suggest cooperative roles for CLCA and TMEM16 proteins in influencing the physiology of multipl

81 tions that alter ion channel activity of the TMEM16 proteins localize around the groove, it was sugge

82 the structure and function understanding of TMEM16 proteins, how mammalian TMEM16 CaPLSases open and

83 domain of Ist2, which bears homology to the TMEM16 proteins, possesses a lipid scramblase activity t

84 blases including bovine rhodopsin and fungal TMEM16 proteins.

85 ly to be a general functional feature of the TMEM16 scramblases and therefore of general importance i

86 TMEM16 scramblases dissipate the plasma membrane lipid a

87 We show that all TMEM16 structures thin the membrane and that the majorit

88 ANO5 is a member of the Anoctamin/TMEM16 superfamily that encodes both ion channels and re

89 y members of the anoctamin (Ano, also called Tmem16) superfamily, but the mechanisms of Ano1 gating b

90 f the TCS superfamily, suggesting that, like TMEM16s, the OSCA/TMEM63 family maintains a conserved po

91 id and ion translocation by Ca(2+)-regulated TMEM16 transmembrane proteins utilizes a membrane-expose