Paper of the Month - June

The synergistic relationship between actin and microtubules plays a crucial role in neuronal maturation.  

The synergistic relationship between actin and microtubules plays a crucial role in neuronal maturation.  

Just like the human body, cells require a skeleton to guide growth, support and movement. This essential ‘cytoskeleton’ is comprised of a particular set of proteins present in all cellular organisms: humans, plants, animals and even bacteria. 

June’s Paper of the Month by Elie et al. focused on the role of a neuronal protein, Tau, and its link to two major cytoskeletal proteins: actin and microtubules. 

These cytoskeletal filaments have a well-established dynamic and synergistic relationship in terms of cellular growth, division and movement. However the molecular basis governing this synergy remains poorly understood, although several proteins have been identified as potential ‘linkers’ between actin and microtubules. As they play a crucial role in cellular function, determining the mechanics of their relationship is fundamental in understanding cellular irregularities and pathologies.

Tau is a neuronal protein known to promote the polymerisation of microtubules along the body of nerve cells and regulate the actin cytoskeleton. As such, it becomes an excellent candidate for further experimentation as a co-organisational protein of actin and microtubules. Elie et al. investigated Tau’s ability to simultaneously organise both proteins. 

Through live Total Internal Reflection Fluorescence (TIRF) microscopy, they found tau induced a bundling effect on actin. Co-sedimentation assays of tau with both cytoskeletal proteins, illustrated tau as a cross-linker between actin and microtubules. Through these cross-links, macro-molecular structures were able to form. 

Microtubule and actin polymerisation is temperature-dependent thus these parameters were strictly controlled. They used the Linkam MC60 warm stage controller to control the temperature parameters for their live TIRF microscopy experiment.

The TIRF microscopy system set up, with the Linkam MC60 controller on the right.  

The TIRF microscopy system set up, with the Linkam MC60 controller on the right.  

Fluorescently labelling proteins is a popular way of visualising protein localisation and interactions. Co-ordination experiments were conducted by fluorescently labelling actin and microtubules. They visualised their concomitant polymerisation and organisation in the presence of fascin – an actin bundling protein – and tau. In presence of fascin they found only actin bundled together with no effect on microtubules or microtubule-actin co-ordination. However in the presence of tau, growing microtubules and actin filaments were found to co-align with each other, confirming tau as a cross-linking protein of these two major cytoskeletal elements. 

Fluorescent labelling of actin and microtubules with fascin on the left and tau on the right. 

Fluorescent labelling of actin and microtubules with fascin on the left and tau on the right. 

Recent studies have highlighted tau protein presence in junctions between neurons. Elie et al., propose that tau may participate in the microtubule/actin coordination that controls synapse formation and function. Uncovering some of the mystery around cytoskeletal organisation will have important medical repercussions. Abnormal tau protein is linked with Alzheimer’s, a neurodegenerative disease. Advancements in understanding such intricate protein relationships may aid in further unearthing the pathways which lead to cytoskeletal pathologies.

Read more:

Linkams interview with Isbelle Arnal.

Elie, A. et al. (2015). Tau co-organizes dynamic microtubule and actin networks. Sci. Rep. 5, 09964

By Tabassum Mujtaba