1. Cell Biology
  2. Developmental Biology
Download icon

Membrane Structures: Cellular fingers take hold

  1. Yukiko M Yamashita  Is a corresponding author
  1. Howard Hughes Medical Institute, University of Michigan, United States
  • Cited 0
  • Views 1,211
  • Annotations
Cite this article as: eLife 2016;5:e19405 doi: 10.7554/eLife.19405


Invaginations in the membranes of embryonic cells appear to orient cell division in sea squirts.

Main text

Cells in textbooks tend to have simple shapes, with surfaces that merely separate the contents of the cell from the outside world. However, this is far from the truth. Sperm cells and nerve cells, for example, have quite complex shapes, and the cell surface can play host to a range of organelles and structures, including primary cilia and a variety of other protrusions from the cell membrane (Singla and Reiter, 2006; Kornberg and Roy, 2014; Gerdes and Carvalho, 2008; Buszczak et al., 2016).

Now, in eLife, Takefumi Negishi, Hitoyoshi Yasuo, Naoto Ueno and colleagues report the discovery of a new membrane structure that forms in the embryos of a marine creature commonly called a sea squirt (Negishi et al., 2016). This structure involves a thin finger-like protrusion from one cell’s membrane inserting itself into a pocket (or invagination) formed in the membrane of the cell in front (Figure 1).

Negishi et al. – who are based at National Institutes of Natural Sciences in Japan and Sorbonne University in France – found that the membrane invagination always projects toward an organelle in the cell known as the centrosome. This organelle serves as an organizing center for protein filaments called microtubules. As such, the centrosome has an integral role in the assembly of the mitotic spindle: the macromolecular machine (composed of microtubules) that segregates the chromosomes during cell division.

Negishi et al. suggest that the invagination holds the centrosome in place to ensure that the mitotic spindle is oriented correctly. This conclusion is based upon three lines of evidence. First, the centrosome is closely connected to the tip of the invagination via microtubules. Second, cutting this tip with a laser caused the invagination to quickly retract, demonstrating that it was under mechanical tension. Third, Negishi et al. show that mutant sea squirts that fail to orient their spindles correctly tended to form the membrane invaginations in the wrong direction as well. These mutants included those with defects in a developmental phenomenon known as “planar cell polarity” (often shortened to PCP), which instructs how animal cells in specific tissues become oriented in the same direction. These findings indicate that the direction in which the invagination forms is under the control of the same signaling pathway that controls planar cell polarity.

This circumstantial evidence is strong. However, Negishi et al. were not able to directly test the role of the invagination in orienting the spindle because it regrew rapidly after being cut with the laser. Confirming that the invagination does indeed anchor the centrosome will require further study, in particular to identify the molecular components that govern how the invagination forms.

Further experiments are also needed to answer a number of other questions. For example, how does the membrane know the position of the centrosome in order to project towards it? Although the microtubules that emanate from the centrosome might provide the cue, this mechanism does not explain how the membrane invagination is carved into a thin finger-like tube. Also, is the composition of the invagination different to that of the rest of the cell surface? And if the answer to this question is yes, is there a barrier that keeps the two membranes distinct (as is the case for the primary cilia; Hu et al., 2010)?

Also, how does the invagination orient the spindle? This remains unclear because, by the time the spindle forms and a cell begins to divide, the invagination (like the primary cilium) has been retracted or otherwise removed (Figure 1). Perhaps, the invagination pulls the centrosome when it retracts as the process of cell division begins.

Membrane invaginations and cell division.

Schematic diagram showing two neighboring cells in the developing embryo of a sea squirt. (A) Before the cells divide an invagination forms in the membrane at the rear (posterior) side of both cells, while a finger-like protrusion forms on the front (anterior) side of each cell and inserts itself into the invagination of the cell in front of it. The tip of the invagination is attached to the centrosome by microtubules. Specifically, the invagination attaches to one of the two centrioles that make up the centrosome – the same centriole that also grows a primary cilium. (B) When the cells begin to divide, the invagination/protrusions and primary cilia have disappeared and the mitotic spindles are oriented along the anterior-posterior axis. Negishi et al. propose that the membrane invagination holds the centrosome to orient the spindle.

Many other membrane protrusions have roles in cell signaling: is this the case for membrane invaginations too? Negishi et al. show that the formation of the invagination is clearly downstream of the PCP signaling pathway (Negishi et al., 2016), so it is tempting to speculate that PCP signaling acts through the invagination itself.

Finally, the membrane invagination discovered by Negishi et al. adds to an expanding list of membrane protrusions and organelles. As such we cannot help but wonder how many similar structures have been missed in the cells of other organisms and therefore are still waiting to be discovered.


Article and author information

Author details

  1. Yukiko M Yamashita

    Life Sciences Institute, Department of Cell and Developmental Biology, Howard Hughes Medical Institute, University of Michigan, Ann Arbor, United States
    For correspondence
    Competing interests
    The author declares that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5541-0216

Publication history

  1. Version of Record published: August 9, 2016 (version 1)


© 2016, Yamashita

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.


  • 1,211
    Page views
  • 101
  • 0

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Cell Biology
    2. Stem Cells and Regenerative Medicine
    Gaspare La Rocca et al.
    Research Article Updated

    Although virtually all gene networks are predicted to be controlled by miRNAs, the contribution of this important layer of gene regulation to tissue homeostasis in adult animals remains unclear. Gain and loss-of-function experiments have provided key insights into the specific function of individual miRNAs, but effective genetic tools to study the functional consequences of global inhibition of miRNA activity in vivo are lacking. Here we report the generation and characterization of a genetically engineered mouse strain in which miRNA-mediated gene repression can be reversibly inhibited without affecting miRNA biogenesis or abundance. We demonstrate the usefulness of this strategy by investigating the consequences of acute inhibition of miRNA function in adult animals. We find that different tissues and organs respond differently to global loss of miRNA function. While miRNA-mediated gene repression is essential for the homeostasis of the heart and the skeletal muscle, it is largely dispensable in the majority of other organs. Even in tissues where it is not required for homeostasis, such as the intestine and hematopoietic system, miRNA activity can become essential during regeneration following acute injury. These data support a model where many metazoan tissues primarily rely on miRNA function to respond to potentially pathogenic events.

    1. Cell Biology
    2. Neuroscience
    Zhong-Jiao Jiang et al.
    Research Article

    TRPM7 contributes to a variety of physiological and pathological processes in many tissues and cells. With a widespread distribution in the nervous system, TRPM7 is involved in animal behaviors and neuronal death induced by ischemia. However, the physiological role of TRPM7 in CNS neuron remains unclear. Here, we identify endocytic defects in neuroendocrine cells and neurons from TRPM7 knockout (KO) mice, indicating a role of TRPM7 in synaptic vesicle endocytosis. Our experiments further pinpoint the importance of TRPM7 as an ion channel in synaptic vesicle endocytosis. Ca2+ imaging detects a defect in presynaptic Ca2+ dynamics in TRPM7 KO neuron, suggesting an importance of Ca2+ influx via TRPM7 in synaptic vesicle endocytosis. Moreover, the short-term depression is enhanced in both excitatory and inhibitory synaptic transmission from TRPM7 KO mice. Taken together, our data suggests that Ca2+ influx via TRPM7 may be critical for short-term plasticity of synaptic strength by regulating synaptic vesicle endocytosis in neurons.