Spatial Organization of Biological Fuctions | BPS Thematic Meeting

Spatial Organization of Biological Functions Meeting

Poster Abstracts

9-POS Board 9 A MAP-PTM CODE THAT ORCHESTRATES LYSOSOMAL REORGANIZATION Deepak M Khushalani 1 ; Joydipta Kar 1 ; Satya Bikash Nayak 1 ; Subhash Chandra Chaudhary 1 ; Nitin Mohan 1 ; 1 Indian Institute of Technology Kanpur (IIT-K), Biological Sciences and Bioengineering, Kanpur, India Lysosomes, often referred to as the “trash bags” of cells, recycle nutrients via endocytic and autophagic pathways. However, in nutrient-rich conditions, they support anabolic functions by hosting mTORC1 on their surface, demonstrating their functional dichotomy. This functional duality is tightly coupled to changes in lysosome positioning: nutrient depletion causes their perinuclear accumulation, while nutrient abundance drives their reorganization toward the cell periphery. Precise spatial organization and transport of lysosomes is essential for maintaining cellular homeostasis and signalling. Microtubule-associated proteins (MAPs) and tubulin post translational modifications (PTMs) together form a regulatory network for motor-driven transport. Yet, the spatial logic by which different motors orchestrate lysosomal reorganization remains elusive. Here, we uncover how MAPs and PTMs generate a combinatorial code that governs lysosome transport dynamics. Using super-resolution imaging, we demonstrate that MAP4 and MAP7D1 selectively partition onto tyrosinated and detyrosinated MT subsets, respectively. This MAP-PTM pairing establishes discrete intracellular routes: MAP4-decorated tracks support kinesin-3 (KIF1A), while MAP7D1-decorated MTs enable kinesin-1 (KIF5B) motility. Correlative live-cell and STORM imaging reveal that MAP density on microtubules dictates the balance between anterograde and retrograde lysosomal movement. Strikingly, both MAP4 overexpression and knockdown trap lysosomes in the perinuclear space and impair their nutrient-responsive remodelling. Together, our findings reveal how spatial compartmentalization of the MT cytoskeleton through MAP-PTM interactions establishes a molecular "traffic code" for lysosome transport and positioning—linking cytoskeletal architecture to functional outcomes. This work provides a conceptual framework for how cells choreograph organelle localization via modular cytoskeletal regulation. Keywords: Microtubules (MT), Microtubule-Associated Proteins (MAPs), Microtubule post-translational modifications (Mt-PTMs), Lysosomes

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