Dynein and kinesin are both responsible for transportation within cells. Dyneins transport cargo towards the minus end of a microtubule (Kon et al., 2012) whilst kinesins transport cargo towards the plus end of a microtubule (Dogan et al., 2015). Dynein is an AAA+ ATPase, it is part of a family of proteins that have a conserved residue-sequence. AAA+ ATPases catalyse hydrolysis of ATP to ADP to undergo mechanical work within the cell (Erzberger and Berger, 2006). Kinesin is structurally similar to myosin as well as G-proteins, suggesting that they share ancestral history (Vale and Milligan, 2000). Dynein and kinesin work as an antagonistic pair for intracellular movement, so loss of one family will pose complications that the eukaryote would need to adapt to accommodate if it is to survive.
Kinesin
Kinesin forms a homodimer proteins when in its active conformation. The dimer is held together by a coiled-coil of tail domains of the two monomers. Each monomer has a head with a microtubule binding site and a nucleotide binding site, a neck linker, and a tail, these make up the heavy chain. The head domain bears gene sequence similarity with myosin (Dogan et al., 2015). The tail domains bind a light chain, which provides substrate specificity but also modularity (Hirokawa et al., 2009). The kinesin superfamily has 14 currently known, each has their own functional niche. The functions of kinesin therefore cannot be pinpointed to a few specific roles, rather there is such a broad range of functions that it is difficult to outline the general themes any more specifically than movement of cargo and structural regulation (Miki et al., 2005). Kinesin moves in a hand-over-hand fashion, moving 80Å forward with each step (Vale and Milligan, 2000). Binding of the microtubule-binding site (MTBS) to the microtubule is mediated by position of the neck linker and presence or absence of ATP in the nucleotide-binding site (NBS). The front head binds the microtubule by its MTBS. The rear head releases the microtubule, and ATP binds the front head NBS. ATP binding causes linker-docking in the front head, changing the orientation of the linker from backward to forward and driving the stepping motion. The free head is pushed forward to become the front head and attaches the microtubule ahead of the now-rear head. ATP cannot bind the new front head until the ATP bound to the rear head is hydrolysed to ADP, causing dissociation from the microtubule. This strictly regulated mechanism prevents both heads from releasing the microtubule at the same time (Dogan et al., 2015).
Dynein
Dynein operates as a dimeric complex, but each monomer of the dimer has 4 subunits; a AAA+ ATPase hexameric ring, coiled-coil stalk, linker and buttress (Carter et al., 2011). The AAA+ ring binds ATP at subunits 1 and 2 using a Walker-A motif (Kon et al., 2004). The stalk domain contains the microtubule-binding site, thus connecting the AAA+ domain to the microtubule. The buttress works almost as a knee for the stalk domain, it communicates conformational changes in the AAA+ domain to the stalk, and acts to move the microtubule binding domain relative to the AAA+ domain (Kon et al., 2012). The regulatory mechanism of microtubule binding and release less well known, and because of this dynein is subject to much more research compared to other motor proteins. Currently the stepping mechanism is thought to come from ATP binding AAA+ subunits 1 and 2 which causes a conformational change to a more regular ring structure. This change in conformation causes the linker to be bent, the MTBS to release the microtubule, and the head of the stalk to move forward relative to the ring. The stalk head moves as the buttress communicates the conformational change of the ring to the stalk, meaning the ring conformational change drives movement of the head and stalk (Carter, 2013; Roberts et al., 2013). The walking motion of dynein is much less ordered than that of kinesins. The dynein superfamily can be split into two categories; cytoplasmic and axonemal, and then into 9 subfamilies within those categories. Cytoplasmic dyneins exist in eukaryotic cells, whereas axonemal dyneins exist within flagella and drive movement of cells. 7 of the 9 families are axonemal dyneins, and remaining 2 are cytoplasmic (Wickstead and Gull, 2007).
Function Loss
At the most primal level of regulation, the cell cycle is controlled by dynein and kinesin. Chromosomes are lined up along the equator of the cell, and upon cytokinesis the sister chromatids are separated through microtubule shortening to draw equal numbers of chromosomes to each pole. Incorrect segregation of chromosomes due to defective motor proteins can have huge knock on effects in humans, potentially even lethality. A study of homozygous dynein heavy chain deletion showed embryonic lethality in mice (Harada et al., 1998). A number of neurological diseases arise as the result of loss of motor protein function, there are links to Alzheimer’s, Parkinson’s and even motor neurone disease (Lipka et al., 2013). Secondly; organelles, vesicles and RNA among many other types of cargo are transported with the use of kinesin and dynein (Holt and Bullock, 2010). On the back of this, it takes little explanation to highlight the breadth and range of severe side-effects that may come about through loss of kinesin or dynein.
Eukaryotic life has already been shown to exist without dynein in higher plants, red algae and Entamoeba, with no genes present that encode transcripts for dynein-like proteins (Wickstead and Gull, 2007). The kinesin subfamily kinesin-14 is able to undergo retrograde transport, thus transporting cargo from the plus end back to the minus end in a similar fashion to dynein (Miki et al., 2005). Arabidopsis has 21 genes encoding retrograde (C-terminal) motor proteins, it is suggested that these genes have undertaken the functions of dynein to allow the plant to survive (Vale, 2003). There is therefore scope for other eukaryotes to evolve and utilise kinesin-14 to undergo dyneins functions of minus end transport in the event of a loss of dynein. Due to a lack of eukaryotes without kinesin, and the sheer number of kinesin families, it can be inferred that kinesin is an incredibly important protein for eukaryotic life. A loss of kinesin could be a step too far for evolution to be able to adapt and recover from, resulting in unviability. Because of the structural and functional similarity between kinesin and myosin (Vale and Milligan, 2000) there is a possibility that myosin may be able to take on the functions of kinesin should it be lost. Myosin does not bind microtubules however, it binds to actin filaments so it can undergo its role in muscular contraction. A change in substrate specificity from actin to microtubules is a relatively small task when compared to reversing dyneins direction of function, and when provided with a large enough selection pressure and the time to adapt. This may not be dynein directly undergoing the functions of kinesin, but could prove enough for life to continue after adaptation.
Dynein has been shown to be the only motor protein that can move long distances along a microtubule towards the minus end (Allan, 2011). This functionality may be of a greater scale than a eukaryotic kinesin-14 could adapt to, if this was the case then it would be impossible for the cell to undergo its normal functions. The species may be unable to survive long enough for evolution to ever takes its course and find a solution to the loss of dynein. Transport distances could potentially adapt to longer paths, but is unlikely to get the chance. Alongside this, dynein has been shown to be essential in mice as stated previously, dynein loss would likely result in loss of cell cycle function and therefore be lethal. Mitotic and meiotic regulation would be affected, likely causing disease if not deletion. It is not too unreasonable to assume that this could have the same effects on other eukaryotic species, and if so the probability that evolution would ever get the chance to try and adapt the functions of kinesin to take on those of dynein is very slim. However, if hypothetically this step were overcome, there is a chance that kinesin-14 could pave the way for new kinesin functionality.
Axonemal dyneins function by sliding of microtubule doublets in relation to other doublets within the flagellum. This results in the flagellum beating in an S-shaped fashion, a process that is highly regulated through the use of second messengers as well as dynein itself (Salathe, 2007). The beating pattern is systematic and uniform, dynein causes lengthening and shortening of one microtubule relative to its partner by sliding at specific points to provide a methodical bending pattern. The direction of sliding is not necessarily the key feature of the movement, the coordination of this movement provides the functionality. A change of motor protein from dynein to kinesin may have little to no effect on the beating pattern as long as the action remains just as ordered. If evolution was given the time to adapt regulation from dynein to kinesin, a total reverse in direction of sliding microtubules would not necessarily pose a problem and the flagellum could very possibly overcome this issue with surprising ease. Salathe states that spermatozoa lacking dynein in its flagellum fail to show hyperactivity in acidic environments, this has the effect of reducing the fitness of sperm to undergo their fertilising function (Salathe, 2007). In the case of this, it then becomes a race between evolution or numbers of the organism rapidly decreasing. It is difficult to predict which of these two would be the resulting outcome, but if evolution were to come out on top there seems to be no reason why flagellum motion would be permanently afflicted.
Final Remarks
In the case of loss of either kinesins or dyneins, there are potential solutions and adaptations that eukaryotes may be able to make to overcome function loss. The most likely scenario of survival in the event of kinesin loss would come from myosin taking over the role of plus ended cargo transport, although this is not directly dynein so may not be applicable to the problem the question poses. In the event of dynein loss it is likely that kinesin-14 could provide a template for protein function, but adaptations would need to be made to its activity as it is not capable of transporting cargo the distances that dynein operates across. There would likely be complications in essential processes of the organism such as cell cycle and fertilisation, arising through chromosomal segregation and sperm motility fitness reductions respectively. Herein, there is then competition between rate of evolutionary adaptations and lack of fitness of the organism causing extinction ultimately. Given the time-period necessary for evolution to adapt, the chances are extinction would come about first, but if such a length of time was available there is a possibility that eukaryotic life could adapt to the loss