Introduction Different channel in the body they come from different families, and can have different function depending where they are found in the body. TRPM2 channel is part of a family called transient receptor channel (TRP) [4], and it can be found in many different part of the body, but we will be concentrating on it in the pancreatic β-cell. This channel can be activated by different molecules such as adenosine diphosphate ribose (ADPR) and many others, and through these molecules secret insulin. On the other hand this channel can lead to diabetes in certain way such as oxidative stress. Furthermore certain pharmacology substance such blocker and drugs can lead to the inhibition of this channel.
What are TRPM2 channel In mammals there …show more content…
TRPM2 channels are multifunctional, Ca2+ permeable channel, and it can be activated by warm temperature [1]
Molecular Structure The human TRPM2 gene is located, on chromosome 21 q 22.3. When TRPM2 is translated into a protein, it will contain 6 transmembrane domains (S1-S6), a pore forming loop is made between S5 and S6 (figure 1) [1]. The TRPM2 channel is assembled into a homo-tetramer, but sometime it can also be assembled into a hetro-tetramer, but in both cases the C- and N-terminus they are orientated into the cytoplasm because they have domains in which molecules can bind to controlling the activation of the TRPM2 channel [1] The C-terminus of this channels it contains coiled-coil character, linker region and most importantly a Adenosine diphosphate ribose (ADPR) pyrophosphates domain or Nudix like domain (it is important in the activation of the TRPM2) (figure 1, appendix) [5] The N-terminus on the other hand contains one domain called the calmodulin (CaM) motif which is important in controlling TRPM2 channel activation, and it also contains 4 homologous domains (figure 1, appendix) …show more content…
In the extracellular space NAD+ ca be found, it can be converted into ADPR or cADPR through a CD38 ectoenzyme [1]
c. In the Mitochondria; H2O2 can enter the cell and go to the mitochondria where it will make ADPR[1]
Once the ADPR has been generated in the cell then it attaches to the NUDT9-H (Nudix like) domain on the C-termini of the TRPM2 channel, which causes TRPM2 channel to open and Ca2+ influx into the cell [1].
If the ADPR was to be made in the extracellular space then ADPR will bind to a plasma receptor that will activate G-protein and PLC, leading to the production of IP3 which cause Ca2+ that is stored in the cell to be released that will increase [Ca2+]I, [1]
2) H2O2 and cADPR, not only can they produce ADPR but they can also bind directly to the TRPM2 channel and cause its activation. For cADPR they can bind to the same domain of ADPR (Nudix domain) (figure 2) [7]
3) Thermosensitivty
TRPM2 channels are war sensitive, meaning at warm temperature such as our body temperature the TRPM2 channel can be activated. So when we are at our body temperature (~ 34oC and ~37oC) the cADPR molecule will activate TRPM2 (by making ADPR) that will cause Ca2+ influx which cause insulin secretion (figure 3) [3,
What are TRPM2 channel In mammals there …show more content…
TRPM2 channels are multifunctional, Ca2+ permeable channel, and it can be activated by warm temperature [1]
Molecular Structure The human TRPM2 gene is located, on chromosome 21 q 22.3. When TRPM2 is translated into a protein, it will contain 6 transmembrane domains (S1-S6), a pore forming loop is made between S5 and S6 (figure 1) [1]. The TRPM2 channel is assembled into a homo-tetramer, but sometime it can also be assembled into a hetro-tetramer, but in both cases the C- and N-terminus they are orientated into the cytoplasm because they have domains in which molecules can bind to controlling the activation of the TRPM2 channel [1] The C-terminus of this channels it contains coiled-coil character, linker region and most importantly a Adenosine diphosphate ribose (ADPR) pyrophosphates domain or Nudix like domain (it is important in the activation of the TRPM2) (figure 1, appendix) [5] The N-terminus on the other hand contains one domain called the calmodulin (CaM) motif which is important in controlling TRPM2 channel activation, and it also contains 4 homologous domains (figure 1, appendix) …show more content…
In the extracellular space NAD+ ca be found, it can be converted into ADPR or cADPR through a CD38 ectoenzyme [1]
c. In the Mitochondria; H2O2 can enter the cell and go to the mitochondria where it will make ADPR[1]
Once the ADPR has been generated in the cell then it attaches to the NUDT9-H (Nudix like) domain on the C-termini of the TRPM2 channel, which causes TRPM2 channel to open and Ca2+ influx into the cell [1].
If the ADPR was to be made in the extracellular space then ADPR will bind to a plasma receptor that will activate G-protein and PLC, leading to the production of IP3 which cause Ca2+ that is stored in the cell to be released that will increase [Ca2+]I, [1]
2) H2O2 and cADPR, not only can they produce ADPR but they can also bind directly to the TRPM2 channel and cause its activation. For cADPR they can bind to the same domain of ADPR (Nudix domain) (figure 2) [7]
3) Thermosensitivty
TRPM2 channels are war sensitive, meaning at warm temperature such as our body temperature the TRPM2 channel can be activated. So when we are at our body temperature (~ 34oC and ~37oC) the cADPR molecule will activate TRPM2 (by making ADPR) that will cause Ca2+ influx which cause insulin secretion (figure 3) [3,