Open Access

Classical dynamin DNM1 and DNM3 genes attain maximum expression in the normal human central nervous system

BMC Research Notes20147:188

https://doi.org/10.1186/1756-0500-7-188

Received: 28 December 2013

Accepted: 24 March 2014

Published: 28 March 2014

Abstract

Dynamin is a super-family of large GTPase proteins that polymerise during their biological activity. Dynamin polymers form around lipid tubes and contribute to the membrane fission and scission of nascent vesicles from parent membranes. Here we used the NCBI Gene Expression Omnibus (GEO) database and the BioGPS gene expression portal to study differential dynamin gene expression in normal human organs or tissues. From the GDS1096 and GDS596 dataset, we downloaded the relative expression levels of dynamin-related genes (presented as percentages), with respect to all of the other genes on the array (platform Affymetrix GPL96), which includes the best characterised human genes. The expression profiles of dynamin in the central nervous system (CNS) are clearly distinct from the expression profiles in the other organs or tissues studied. We found that the classical dynamin DNM1 and DNM3 genes reach their maximum expression levels (100% of maximal expression) in all normal human CNS tissues studied. This is in contrast to the expression profile in the other normal human organs or tissues studied, in which both dynamin DNM1 and DNM3 genes showed approximately 50% maximal expression. This data mining analysis supports the concept that there is a relationship between the synapse and the molecular function of dynamin, suggesting a new field of work in the study of neurodegenerative diseases.

Keywords

Dynamin Central nervous system Gene expression Data mining

Discussion

We have focused our attention on the expression profiling of dynamin genes in several normal human organs or tissues, using the NCBI Gene Expression Omnibus (GEO) database. We have chosen to study dynamin genes because dynamin is a super-family of GTP-binding mechanochemical proteins that are involved in fundamental processes, such as the scission of nascent vesicles from parent membranes and mitochondrial fusion and/or fission[1]. In addition, we believe that the dynamin super-family is a biological system suitable for studying differential gene expression in organs or tissues.

Specifically, we considered the group of genes coding the following protein families within the dynamin super-family[2]: (i) the classical dynamins and dynamin-like proteins that tubulate and sever membranes and are involved in clathrin-mediated endocytosis and other vesicular trafficking processes (DNM1, DNM1L, DNM2, DNM3); (ii) the guanylate-binding proteins, which are induced by type II interferons and anti-inflammatory cytokines (GBP1 and GBP2); (iii) the proteins on the outside of the outer mitochondrial membrane that participate in mitochondrial fusion and contribute to the maintenance and function of the mitochondrial network (MFN1 and MFN2); (iv) proteins in the mitochondrial inter membrane space that are involved in mitochondrial fusion, and in which mutations in the gene are associated with optic atrophy type 1 (OPA1); and (v) Mx proteins, which are involved in resistance against viral infections (MX1 and MX2). Taken together, these proteins constitute a large set of GTPase proteins that polymerise within each group or family according to the dynamin molecular function[3]. These dynamin polymers (such as rings and helices) are formed around lipid tubes and contribute to membrane fission[4].

To address this issue, we relied on the independent studies by Su A.I. et al.[5] (GDS596) and Ge X. et al.[6] (GDS1096). We downloaded the relative expression levels of dynamin-related genes (presented as percentages) with respect to all other genes on the array from these NCBI-GEO database records. It is important to note that both NCBI-GEO data sets were created based on the same array platform (Affymetrix GPL96), which include all the best characterised human genes. Figure 1 shows the profiles of dynamin gene expression levels (expressed as percentage and presented as beam shaped lines) in samples from normal human organs or tissues that are common to the NCBI-GEO records of both studies. From a strict visual analysis of these beam lines, the data can be separated into two consistent populations or sub-beam lines of expression profiles, one of which groups together the profiles corresponding to components of the central nervous system (CNS) (Figure 2). This data mining analysis allowed us characterise dymanin gene expression trends in the CNS. We found clear evidence that the classical dynamin DNM1 and DNM3 genes reach their maximum expression level (100% measurement score) in all of the normal human CNS tissues studied. Moreover, this results is in contrast to the expressionprofiles observed in the other normal human organs and tissues studied, in which both the dynamin DNM1 and DNM3 genes showed approximately 50%. A detailed breakdown of the data is presented in Table 1. To improve the rigor of our analysis, we used the BioGPS gene expression portal[7, 8] to explore the expression profiles of human dynamin-retaled genes. We found that the classical dynamin DNM1 and DNM3 genes are also maximally expressed in normal human CNS components and at significantly lower level in others organs or tissues[9, 10].
Figure 1

Data retrieved from the dataset records GDS596 and GDS1096 of NCBI-GEO database. The figure depicts the dynamin expression profiles of several normal human organs or tissues. The dynamin genes are listed on the x-axis, while, the relative gene expression is shown on the y-axis. The points represent the gene expression level (presented as a percentatge). Each point represents the mean of the gene expression level in normal organ or tissue samples that were common to both of the independent experimental datasets (GDS596 and GDS1096) of the NCBI-GEO database. According to the NCBI-GEO data analysis, all values within an array are rank ordered and then placed into percentile ‘bins’. In other words, all the values of one hybridisation are sorted and then split into 100 groups. Thus, the points give an indication of where the expression of a given gene falls with respect to all genes on that array. In these records, the platform GPL96 (Affymetrix Human Genome U133A Array) were used, that includes over 1,000,000 unique oligonucleotide features covering more than 39,000 transcript variants, which in turn represent more than 33,000 of the best characterised human genes. See Table 1 for a detailed specification of the data.

Figure 2

Dynamin expression profiling in representative components of normal human CNS tissues and organs. Data retrieved from Figure 1. This figure depicts the expression profiling of the representative components of the CNS. The genes studied are denoted along the x-axis and the gene expression (presented as a percentatge) on the y-axis. The Figure 1 legend explains how to interpret the NCBI-GEO profile charts.

Table 1

Relative gene expression profiles from normal human organs and tissues (presented as percentatges)

Organ-tissue

DNM1 (215116_s_at)

DNM1L (203105_s_at)

DNM2 (202253_s_at)

DNM3 (209839_at)

GBP1 (202269_x_at)

GBP2 (202748_at)

MFN1 (211801_x_at)

MFN2 (201155_s_at)

MX1 (202086_at)

MX2 (204994_at)

OPA1 (212213_x_at)

Amygdala

99

67

55

96

8

35

64

89

74

68

92

Brain foetal

95

55

50

91

15

31

65

87

68

67

85

Brain whole

99

52

64

94

1

35

54

92

78

70

88

Caudate nucleus

98

67

67

97

10

42

62

92

77

71

94

Cerebellum

99

47

64

96

2

35

60

93

71

66

79

Hippocampus

98

69

52

97

20

48

59

92

82

71

92

Hypothalamus

98

69

60

97

22

49

64

92

90

75

91

Spinal cord

93

56

65

94

46

51

59

91

84

63

91

Thalamus

99

71

55

98

17

38

64

93

82

70

91

Adrenal gland

44

42

72

56

43

77

53

88

78

73

74

Bone marrow

47

22

73

47

8

63

58

93

81

85

77

Heart

52

54

68

46

26

64

64

98

81

81

87

Kidney

59

51

78

40

39

67

55

88

75

71

74

Liver

52

27

68

48

56

55

50

91

83

81

76

Lung

51

35

76

44

61

75

62

88

86

84

72

Lung foetal

67

50

73

40

50

59

63

83

70

71

72

Ovary

35

35

49

53

43

83

61

88

71

73

84

Pancreas

63

46

59

34

25

56

72

87

74

81

74

Pituitary

91

65

55

83

29

49

58

88

81

70

87

Placenta

38

49

69

35

58

66

61

83

73

73

70

Prostate

52

50

69

38

52

68

54

86

75

71

79

Salivary gland

57

43

57

46

38

71

50

89

80

82

73

Skin

75

33

49

57

35

77

72

91

59

76

84

Testis

52

62

71

47

14

62

61

89

64

74

70

Thymus

47

41

72

45

61

74

62

86

88

88

70

Thyroid

49

42

75

36

80

70

63

89

85

79

83

Trachea

64

35

65

45

63

70

64

87

84

83

79

Uterus

71

55

60

47

81

82

65

82

72

77

82

Data are presented as the mean values of the dynamin gene expression percentatges calculated from the individual values of the samples common to both NCBI-GEO records (GDS596 and GDS1096). The GPL96 Affymetrix probe set ID is displayed in parentheses below the gene symbol. Where there is more than one entry for the same gene, we selected the entry for which the Affymetrix probe set ID refers to the mRNA or coding DNA sequence (cds). The CNS tissues and organs are shown in the top block of the table. DNM1 and DNM3 gene expression values are shown in bold. See the legend of Figure 1.

The CNS consists of the brain and spinal cord, where synapses are the dynamic structures through which all nervous system signals traverse. Dynamin polymerisation in membrane fission is thought to play a significant role in the synapse (Gene Ontology GO:0003373) which is suggestive of the concept of a relationship between synapses and dynamins[11]. Several animal model studies have shown that dynamin genes are highly expressed in neurons[1215]. In conclusion, based on their high levels of expression in human CNS, DNM1 and DNM3 can be considered as CNS-specific dynamin genes, at least in the following human CNS components: amygdala, foetal brain, whole brain, caudate nucleus, cerebellum, cerebellum peduncles, cingulate cortex, globus pallidus, hippocampus, hypothalamus, medulla oblongata, occipital lobe, parietal lobe, pineal day, pineal night, pons, prefrontal cortex, spinal cord, subthalamic nucleus, temporal lobe, and thalamus. We suggest that the role of dynamins in the CNS could be a potentially interesting area for further biochemical research in neurodegenerative diseases.

Declarations

Acknowledgements

This study was supported by a grant from the “Ministerio de Economia y Competitivdad” of the Spanish Government (AGL 2008-00387/ALI).

Authors’ Affiliations

(1)
Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Rovira i Virgili University

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Copyright

© Romeu and Arola; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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