Dynactin

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Dynactin or Dynein activator complex is a multi-subunit protein found in eukaryotic cells that aids in bidirectional intracellular transport by binding to dynein and kinesin-2 and linking them to the organelle or vesicle to be transported.[1][2]

Structure and mechanism of action

Dynactin
Identifiers
Symbol Dynactin
Pfam PF12455
InterPro IPR022157
Dynamitin
Identifiers
Symbol Dynamitin
Pfam PF04912
InterPro IPR006996
Dynactin subunit p22
Identifiers
Symbol Dynactin_p22
Pfam PF07426
InterPro IPR009991
Dynactin p62 family
Identifiers
Symbol Dynactin_p62
Pfam PF05502
InterPro IPR008603

Dynactin consists of many subunits of which the p150Glued protein (encoded by the DCTN1 gene) is the largest and has been found to be essential for function.[1] This structure of dynactin is highly conserved in vertebrates. There are three isoforms encoded by a single p150Glued gene.[3] The dynactin complex visualized by deepetch electron microscopy appears as a short filament 37-nm in length, which resembles F-actin, plus a thinner, laterally oriented filament that terminates in two globular heads.[4]

The dynactin complex consists of three major structural domains: (1) sidearm-shoulder: DCTN1, DCTN2/dynamitin, DCTN3/p22/p24;(2)the Arp1 rod: Arp1/centractin, actin, CapZ; and (3) the pointed end complex: Actr10/Arp11, DCTN4/p62, DCTN5/p25, and DCTN6/p27.[5] Dynactin interacts with dynein directly by the binding of dynein intermediate chains with p150Glued.[6] DCTN2 (dynamitin) is also involved in anchoring microtubules to centrosomes and may play a role in synapse formation during brain development.[7] DCTN4 (p62) binds directly to the Arp1 subunit of dynactin.[8][9] Arp1 has been shown as the domain for dynactin binding to membrane vesicles (such as Golgi or late endosome) through its association with β-spectrin.[10][11][12][13] The pointed end complex (PEC) has been shown to be involved in selective cargo binding. PEC subunits p62/DCTN4 and Arp11/Actr10 are essential for dynactin complex integrity and dynactin/dynein targeting to the nuclear envelope before mitosis.[14][15][16] Dynactin p25/DCTN5 and p27/DCTN6 are not essential for dynactin complex integrity, but are required for early and recycling endosome transport during the interphase and regulation of the spindle assembly checkpoint in mitosis.[16][17][18]

Functions

Dynactin is often essential for dynein activity[1][19] and can be thought of as a "dynein receptor"[6] that modulates binding of dynein to cell organelles which are to be transported along microtubules.[20][21] Dynactin also enhances the processivity of cytoplasmic dynein[22] and kinesin-2 motors.[23] Dynactin is involved in various processes like chromosome alignment and spindle organization[24] in cell division.[25] Dynactin contributes to mitotic spindle pole focusing through its binding to nuclear mitotic apparatus protein (NuMA).[26][27] Dynactin also targets to the kinetochore through binding between DCTN2/dynamitin and zw10 and has a role in mitotic spindle checkpoint inactivation.[28][29] During prometaphase, dynactin also helps target polo-like kinase 1 (Plk1) to kinetochores through cyclin dependent kinase 1 (Cdk1)-phosphorylated DCTN6/p27, which is involved in proper microtubule-kinetochore attachment and recruitment of spindle assembly checkpoint protein Mad1.[18] In addition, dynactin has been shown to play an essential role in maintaining nuclear position in Drosophila,[30] zebrafish[31] or in different fungi.[32][33] Dynein and dynactin concentrate on the nuclear envelope during the prophase and facilitate nuclear envelope breakdown via its DCTN4/p62 and Arp11 subunits.[16][34] Dynactin is also required for microtubule anchoring at centrosomes and centrosome integrity.[35] Destabilization of the centrosomal pool of dynactin also causes abnormal G1 centriole separation and delayed entry into S phase, suggesting that dynactin contributes to the recruitment of important cell cycle regulators to centrosomes.[36] In addition to transport of various organelles in the cytoplasm, dynactin also links kinesin II to organelles.[2]

See also

References

  1. ↑ 1.0 1.1 1.2 Lua error in package.lua at line 80: module 'strict' not found.
  2. ↑ 2.0 2.1 Lua error in package.lua at line 80: module 'strict' not found.
  3. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  4. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ 6.0 6.1 Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  9. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  10. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  11. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  12. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  13. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  14. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  15. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  16. ↑ 16.0 16.1 16.2 Lua error in package.lua at line 80: module 'strict' not found.
  17. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  18. ↑ 18.0 18.1 Lua error in package.lua at line 80: module 'strict' not found.
  19. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  20. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  21. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  22. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  23. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  24. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  25. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  26. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  27. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  28. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  29. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  30. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  31. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  32. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  33. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  34. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  35. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  36. ↑ Lua error in package.lua at line 80: module 'strict' not found.

Further reading

  • Lua error in package.lua at line 80: module 'strict' not found.

This article incorporates text from the public domain Pfam and InterPro IPR008603

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