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Updated: Jun 23, 2026
Live-imaging of the Drosophila Pupal Eye
Published on: January 12, 2015
LKB1 regulates polarity remodeling and adherens junction formation in the Drosophila eye
Nancy Amin1, Afifa Khan, Daniel St Johnston
1Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, Canada M5G 1X5.
Abstract:
The serine-threonine kinase LKB1 regulates cell polarity from Caenorhabditis elegans to man. Loss of lkb1 leads to a cancer predisposition, known as Peutz-Jeghers Syndrome. Biochemical analysis indicates that LKB1 can phosphorylate and activate a family of AMPK- like kinases, however, the precise contribution of these kinases to the establishment and maintenance of cell polarity is still unclear. Recent studies propose that LKB1 acts primarily through the AMP kinase to establish and/or maintain cell polarity. To determine whether this simple model of how LKB1 regulates cell polarity has relevance to complex tissues, we examined lkb1 mutants in the Drosophila eye. We show that adherens junctions expand and apical, junctional, and basolateral domains mix in lkb1 mutants. Surprisingly, we find LKB1 does not act primarily through AMPK to regulate cell polarity in the retina. Unlike lkb1 mutants, ampk retinas do not show elongated rhabdomeres or expansion of apical and junctional markers into the basolateral domain. In addition, nutrient deprivation does not reveal a more dramatic polarity phenotype in lkb1 photoreceptors. These data suggest that AMPK is not the primary target of LKB1 during eye development. Instead, we find that a number of other AMPK-like kinase, such as SIK, NUAK, Par-1, KP78a, and KP78b show phenotypes similar to weak lkb1 loss of function in the eye. These data suggest that in complex tissues, LKB1 acts on an array of targets to regulate cell polarity.
Insights
The serine-threonine kinase LKB1 is crucial for cell polarity. In complex tissues like the Drosophila eye, LKB1 regulates cell polarity through multiple targets, not primarily AMPK, challenging previous models.
Area of Science:
- Cell Biology
- Developmental Biology
- Genetics
Background:
- The serine-threonine kinase LKB1 (Liver kinase B1) is a key regulator of cell polarity across species.
- Loss of LKB1 function is associated with Peutz-Jeghers Syndrome, a cancer predisposition disorder.
- While LKB1 is known to phosphorylate and activate AMP-activated protein kinase (AMPK)-like kinases, its precise role in cell polarity, particularly in complex tissues, remains incompletely understood.
Purpose of the Study:
- To investigate the role of LKB1 in establishing and maintaining cell polarity within complex tissues.
- To determine if LKB1 primarily acts through AMPK to regulate cell polarity in the Drosophila retina.
- To identify alternative targets of LKB1 involved in cell polarity regulation in the eye.
Main Methods:
- Analysis of lkb1 mutants in the Drosophila eye.
- Phenotypic characterization of adherens junctions and domain organization in photoreceptors.
- Comparison of lkb1 mutant phenotypes with ampk mutants.
- Assessment of polarity under nutrient deprivation conditions.
Main Results:
- Lkb1 mutants exhibit expanded adherens junctions and intermixing of apical, junctional, and basolateral domains.
- Contrary to expectations, ampk mutants do not display the same polarity defects as lkb1 mutants.
- Nutrient deprivation does not exacerbate polarity defects in lkb1 photoreceptors, suggesting AMPK is not the primary mediator.
- Other AMPK-like kinases (SIK, NUAK, Par-1, KP78a, KP78b) show phenotypes consistent with a role in LKB1-mediated polarity.
Conclusions:
- LKB1 does not primarily act through AMPK to regulate cell polarity in the Drosophila retina.
- In complex tissues, LKB1 likely regulates cell polarity by targeting an array of AMPK-like kinases.
- These findings challenge the simplified model of LKB1 function and highlight the complexity of polarity regulation in vivo.
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