This is a timely review on the intracellular transport in neurons, which is a fundamental process for neuronal morphogenesis, function, and survival. It is written from a newly considered mechanistic point of view of what kind of motors are involved in transports of specific cargoes—such as the various kinds of membranous organelles, protein complexes, and mRNA important for neuronal function—and of how each cargo is specifically recognized by the molecular interaction with motor proteins and how that interaction leads to the directional transport.

“Our review focused on the functions of each motor to transport various cargoes such as synaptic vesicle materials, plasma membrane materials, mitochondria, receptors for chemical transmitters, and mRNAs.”

This selective, intracellular transport mechanism plays a significant role, not only in the function of individual neurons at the cellular level, but also on brain wiring, brain development, and higher brain functions, such as memory and learning. This mechanism is common to virtually every process currently under investigation in the field of neuroscience.

Furthermore, because a similar mechanism exists in all kinds of tissues and cells in the human body, this article will be of interest to a wide variety of researchers in the life science fields.

The review is based on the recent discoveries of new kinesin superfamily proteins, KIFs, and a detailed understanding of the important functions of each motor and the unique interactions of molecular motor proteins and their cargo—including various membranous organelles, protein complexes, and mRNAs. These findings were revealed by utilizing a wide variety of techniques in cell and molecular biology, and also the inclusion of knockout and transgenic mice. This review also represents a new way of synthesis on how neurons selectively achieve the directional transport of cargoes.

Nerve cells have long extensions, called dendrites and axons. The impulses of the nerve cells are received at the dendrites from the sensory organs or nerve cells and then transmitted through the axon to the next nerve cells or muscle.

The axons of nerve cells in the spinal cord reach the tip of the toe; therefore the length of a single axon can be quite long.

Many materials need to be transported from the nerve cells to the farthest end of the axons or dendrites in order for the nerve cells to function properly. Therefore, the transport process is fundamental for the function and survival of nerve cells, and the process is regulated in a very precise and intricate manner.

To begin with, the process needs to be directional, and cargoes that need to be transported to the axons and dendrites must be sorted out properly. However, how the directional transport is achieved has not been clearly understood. In recent years, it has become increasingly clear that nerve cells have many motor molecules, especially kinesin superfamily proteins. KIFs and different motor molecules recognize different cargo molecules.

It has also become increasingly clear that these newly found motor molecules must be playing fundamental roles in the directional transport within the nerve cells. Our review focused on the functions of each motor to transport various cargoes such as synaptic vesicle materials, plasma membrane materials, mitochondria, receptors for chemical transmitters, and mRNAs.

Our review also concentrated on the new findings of the molecular recognition of motor molecules and their cargoes, and we have discussed the mechanisms of directional transport from these aspects.

Our review also uncovered that the transport by motors play a significant role in a wide variety of important phenomena such as brain wiring, brain development, and higher brain functions. This means molecular motors are fundamental to the whole field of neuroscience.

Further, because a similar transport mechanism works in all kinds of tissues and cells in our body, intracellular transport by KIFs is fundamentally significant even for fields such in the life sciences.

More than 25 years ago, I observed the fine structure of the axons of nerve cells by using an electron microscopic technique called the "quick-freeze/deep-etch method,"—which enables you to observe inside the cell three-dimensionally at a nanometer-scale resolution.

I also revealed the molecular structure of the kinesin molecule, the first motor molecule to be identified for the transport within an axon. However, right from the beginning, I thought that there were many different shapes of motor molecules and many different kinds of cargoes transported at distinct velocities inside the axon. The kinesin alone could not account for the axonal transport.

Therefore, I undertook the cloning of motor molecules related to kinesin, which is now known as kinesin superfamily proteins, or KIFs. Initially I identified 10 new members of KIFs. I have now identified all 45 kif genes in mammalian organisms such as the human and the mouse.

I used a wide variety of techniques, including cell biology, molecular biology, transgenic mice, knockout mice, biophysical methods. I also used several processes from the field of structural biology—such as cryogenic electron microscopy and X-ray crystallography—in order to reveal the functions, structures, and mechanism of motility.

The obstacles and challenges were such that you always needed to develop and use the very best aspects of each new technique. It also takes a very long time to prepare a paper of the very highest quality.