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Formation of helical membrane tubes around microtubules by single-headed kinesin KIF1A.

Oriola D, Roth S, Dogterom M, Casademunt J - Nat Commun (2015)

Bottom Line: Its single-headed form is known to be very inefficient due to the presence of a diffusive state in the mechanochemical cycle.Remarkably, not only KIF1A motors are able to extract tubes but they feature a novel phenomenon: tubes are wound around microtubules forming tubular helices.Hence, we conclude that KIF1A is a genuinely cooperative motor, possibly explaining its specificity to axonal trafficking.

View Article: PubMed Central - PubMed

Affiliation: Departament d'Estructura i Constituents de la Matèria, Facultat de Física, Universitat de Barcelona, Avinguda Diagonal 647, E-08028 Barcelona, Spain.

ABSTRACT
The kinesin-3 motor KIF1A is in charge of vesicular transport in neuronal axons. Its single-headed form is known to be very inefficient due to the presence of a diffusive state in the mechanochemical cycle. However, recent theoretical studies have suggested that these motors could largely enhance force generation by working in teams. Here we test this prediction by challenging single-headed KIF1A to extract membrane tubes from giant vesicles along microtubule filaments in a minimal in vitro system. Remarkably, not only KIF1A motors are able to extract tubes but they feature a novel phenomenon: tubes are wound around microtubules forming tubular helices. This finding reveals an unforeseen combination of cooperative force generation and self-organized manoeuvreing capability, suggesting that the diffusive state may be a key ingredient for collective motor performance under demanding traffic conditions. Hence, we conclude that KIF1A is a genuinely cooperative motor, possibly explaining its specificity to axonal trafficking.

No MeSH data available.


Related in: MedlinePlus

Mean-field description of helical tube formation.(a) Dimensionless on-axis velocity of the tube respect to  for different φ and a2/l2=0.4. We notice the apparition of long tails in the velocity–force relationship for decreasing φ. (b) Angle dependence on the force per motor  for different a2/l2 values and φ=0.5. (c) Experimental angle distribution of 57 standing helical nanotubes. (d) Angle dependence on the force per motor  for different φ values and a2/l2=0.4. θ=81°, =0.15 pN and a1/l1=0.2. Angles are shown in radians.
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f4: Mean-field description of helical tube formation.(a) Dimensionless on-axis velocity of the tube respect to for different φ and a2/l2=0.4. We notice the apparition of long tails in the velocity–force relationship for decreasing φ. (b) Angle dependence on the force per motor for different a2/l2 values and φ=0.5. (c) Experimental angle distribution of 57 standing helical nanotubes. (d) Angle dependence on the force per motor for different φ values and a2/l2=0.4. θ=81°, =0.15 pN and a1/l1=0.2. Angles are shown in radians.

Mentions: where is the effective force per motor and φ ≡ N1/N2. On the other hand, we know that . By equating the last expression and equation (1), we obtain a transcendental equation for ζ which can be solved numerically. The dynamics of a helical tube and the angle selection are crucially affected by the phenomenological parameter φ. In Fig. 4a, for φ=1, the on-axis velocity–force relationship is linear and ζ is independent of the extraction force F. However, for φ<1, long tails appear on the on-axis velocity–force relationship and ζ becomes strongly dependent on F (Fig. 4b,d). In the latter case, the on-axis velocity may decrease by a factor four under moderately large forces, consistently with our tube-pulling data in comparison with gliding assays (see Methods). In Fig. 4c the experimental angle distribution is shown by taking the average angle of 57 helical tubes. We compare the data with the dependence of ζ on for different values of φ (Fig. 4d). Considering in the experiments, the range φ≃0.6–1.2 approximately bounds the experimental angle values. We can also infer the total off-axis force exerted by the motors Foff and N2 using energetic arguments (Supplementary Note 1), which leads to the lower bound Foff ≃0.04–2 pN and N2≳1–50 motors. On the other hand, surprisingly no helical tube retractions were observed. This fact may be a signature of the long tails in the velocity–force curves as shown in Fig. 4a, and consequently an indirect evidence that typically φ<1.


Formation of helical membrane tubes around microtubules by single-headed kinesin KIF1A.

Oriola D, Roth S, Dogterom M, Casademunt J - Nat Commun (2015)

Mean-field description of helical tube formation.(a) Dimensionless on-axis velocity of the tube respect to  for different φ and a2/l2=0.4. We notice the apparition of long tails in the velocity–force relationship for decreasing φ. (b) Angle dependence on the force per motor  for different a2/l2 values and φ=0.5. (c) Experimental angle distribution of 57 standing helical nanotubes. (d) Angle dependence on the force per motor  for different φ values and a2/l2=0.4. θ=81°, =0.15 pN and a1/l1=0.2. Angles are shown in radians.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4557341&req=5

f4: Mean-field description of helical tube formation.(a) Dimensionless on-axis velocity of the tube respect to for different φ and a2/l2=0.4. We notice the apparition of long tails in the velocity–force relationship for decreasing φ. (b) Angle dependence on the force per motor for different a2/l2 values and φ=0.5. (c) Experimental angle distribution of 57 standing helical nanotubes. (d) Angle dependence on the force per motor for different φ values and a2/l2=0.4. θ=81°, =0.15 pN and a1/l1=0.2. Angles are shown in radians.
Mentions: where is the effective force per motor and φ ≡ N1/N2. On the other hand, we know that . By equating the last expression and equation (1), we obtain a transcendental equation for ζ which can be solved numerically. The dynamics of a helical tube and the angle selection are crucially affected by the phenomenological parameter φ. In Fig. 4a, for φ=1, the on-axis velocity–force relationship is linear and ζ is independent of the extraction force F. However, for φ<1, long tails appear on the on-axis velocity–force relationship and ζ becomes strongly dependent on F (Fig. 4b,d). In the latter case, the on-axis velocity may decrease by a factor four under moderately large forces, consistently with our tube-pulling data in comparison with gliding assays (see Methods). In Fig. 4c the experimental angle distribution is shown by taking the average angle of 57 helical tubes. We compare the data with the dependence of ζ on for different values of φ (Fig. 4d). Considering in the experiments, the range φ≃0.6–1.2 approximately bounds the experimental angle values. We can also infer the total off-axis force exerted by the motors Foff and N2 using energetic arguments (Supplementary Note 1), which leads to the lower bound Foff ≃0.04–2 pN and N2≳1–50 motors. On the other hand, surprisingly no helical tube retractions were observed. This fact may be a signature of the long tails in the velocity–force curves as shown in Fig. 4a, and consequently an indirect evidence that typically φ<1.

Bottom Line: Its single-headed form is known to be very inefficient due to the presence of a diffusive state in the mechanochemical cycle.Remarkably, not only KIF1A motors are able to extract tubes but they feature a novel phenomenon: tubes are wound around microtubules forming tubular helices.Hence, we conclude that KIF1A is a genuinely cooperative motor, possibly explaining its specificity to axonal trafficking.

View Article: PubMed Central - PubMed

Affiliation: Departament d'Estructura i Constituents de la Matèria, Facultat de Física, Universitat de Barcelona, Avinguda Diagonal 647, E-08028 Barcelona, Spain.

ABSTRACT
The kinesin-3 motor KIF1A is in charge of vesicular transport in neuronal axons. Its single-headed form is known to be very inefficient due to the presence of a diffusive state in the mechanochemical cycle. However, recent theoretical studies have suggested that these motors could largely enhance force generation by working in teams. Here we test this prediction by challenging single-headed KIF1A to extract membrane tubes from giant vesicles along microtubule filaments in a minimal in vitro system. Remarkably, not only KIF1A motors are able to extract tubes but they feature a novel phenomenon: tubes are wound around microtubules forming tubular helices. This finding reveals an unforeseen combination of cooperative force generation and self-organized manoeuvreing capability, suggesting that the diffusive state may be a key ingredient for collective motor performance under demanding traffic conditions. Hence, we conclude that KIF1A is a genuinely cooperative motor, possibly explaining its specificity to axonal trafficking.

No MeSH data available.


Related in: MedlinePlus