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Microtubule-Associated Proteins (MAPs): Life’s Mini Conveyor Belts

Contributed by Allison Curley, Ph.D.

As their name suggests, microtubule-associated proteins (MAPs) are a family of proteins that reversibly interact with microtubules, a critical component of the cellular cytoskeleton. Composed of the protein tubulin, microtubules provide structural support, contribute to cell motility and mitosis, and serve as “conveyor belts” that transport vesicles, organelles, and other cellular components throughout the cytoplasm1. MAPs are a heterogeneous group of proteins that were originally identified in brain extracts based on their ability to co-purify with tubulin2. The “classic” and best-characterized MAPs are the structural proteins that promote tubulin polymerization and stabilize microtubules, and are regulated by phosphorylation3. In addition, the term MAP is also often extended to include enzymatically-active proteins such as the microtubule motors kinesin and dynein that move along microtubules by hydrolyzing ATP.             

On the basis of their microtubule interaction motif, most structural MAPs belong to either the MAP1A/1B or the MAP2/Tau family, and key players are described below4, 5. MAP1A is predominantly expressed in the dendrites of adult neurons where it is important for dendrite formation, while MAP1B is mainly expressed in the axons of developing neurons and plays a role in axonal outgrowth6. Another member of the MAP1A/1B family, MAP1S, is expressed in a variety of neuronal and non-neuronal tissues where it anchors the microtubule-organizing center to the centrosome during mitosis7, 8. MAP2 is preferentially expressed in neurons, is important for crosslinking adjacent microtubules, and shares some functional redundancy with MAP1B9. It also interacts with F-actin, in a process thought to promote neurite outgrowth10. Tau is primarily found in axons and also shares some redundancy with MAP1B4. A hyperphosphorylated form of tau has been implicated in the pathology of Alzheimer disease11. The MAP2/Tau family also includes the neuronal and non-neuronal MAP4, important for cell division12.

 

Detection of human EB1 (red) in FPPE prostate carcinoma.

Detection of human EB1 (red) in FPPE prostate carcinoma. Antibody: Rabbit anti-EB1 (IHC-00674). Secondary: DyLight® 594-conjugated goat anti-rabbit IgG (A120-201D4). Counterstain: DAPI (blue).


 

Detection of human MAP1S in FFPE testicular seminoma by IHC.

Detection of human MAP1S in FFPE testicular seminoma by IHC. Antibody: Rabbit anti-MAP1S (A302-815A). Secondary: HRP-conjugated goat anti-rabbit IgG (A120-501P). Substrate: DAB.

 

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References

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2. Borisy GG, Marcum JM, Olmstead JB, Murphy DB, Johnson KA. 1975. Purification of tubulin and associated high molecular weight proteins from porcine brain and characterization of microtubule assembly in vitro. Ann N Y Acad Sci. Jun 20;253:107-132.

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5. Maccioni RB, Cambiazo V. 1995. Role of microtubule-associated proteins in the control of microtubule assembly. Physiol Rev. Oct;75(4):835-864.

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7. Orbán-Németh Z, Simader H, Badurek S, Tranciková A, Propst F. 2005. Microtubule-associated protein 1S, a short and ubiquitously expressed member of the microtubule-associated protein 1 family. J Biol Chem. Jan 21;280(3):2257-2265.

8. Dallol A, Cooper WN, Al-Mulla F, Agathanggelou A, Maher ER, Latif F. 2007. Depletion of the Ras association domain family 1, isoform A-associated novel microtubule-associated protein, C19ORF5/MAP1S, causes mitotic abnormalities. Cancer Res. Jan 15;67(2):492-500.

9. Conde C, Cáceres A. 2009. Microtubule assembly, organization and dynamics in axons and dendrites. Nat Neurosci. May;10(5):319-332.

10. Roger B, Al-Bassam J, Dehmelt L, Milligan RA, Halpain S. 2004. MAP2c, but not tau, binds and bundles F-actin via its microtubule binding domain. Curr Biol. Mar 9;14(5):363-371.

11. Lee VM, Balin BJ, Otvos L, Trojanowski JQ. 1991. A68: a major subunit of paired helical filaments and derivatized forms of normal Tau. Science. Feb 8;251(4994):675-678.

12. Chang W, Gruber D, Chari S, Kitazawa H, Hamazumi Y, Hisanaga S, Bulinski JC. 2001. Phosphorylation of MAP4 affects microtubule properties and cell cycle progression. J Cell Sci. Aug;114(Pt 15):2879-2887.